University of Edinburgh
The relationship between vitamin D status and leukocytes in hospitalised catsTitmarsh, H.F,1 Cartwright J.A1, Kilpatrick, S.1, Gaylor, D1., Milne E 1 Berry, J2., Bommer, N1., Gunn-Moore, D1., Reed, N1., Handel, I. 1, Mellanby, R.J1. *Royal (Dick) School of Veterinary Studies and The Roslin Institute, The University of Edinburgh, Roslin, Midlothian, United KingdomSpecialist Assay Laboratory (Vitamin D), Clinical Biochemistry, Manchester Royal Infirmary, Manchester, United KingdomCorresponding author:Helen Titmarsh BVetMed(Hons)MRCVSHospital for Small AnimalsRoyal (Dick) School of Veterinary StudiesEaster Bush CampusThe University of EdinburghRoslinMidlothianEmail s1066694@sms.ed.ac.uk0131 650 7650Keywords: 25 hydroxyvitamin D, neutrophils, vitamin D, catAbstract Objectives: Vitamin D deficiency, as assessed by serum 25 hydroxyvitamin D (25(OH)D) concentrations, has been linked to markers of systemic inflammation in human and canine medicine. However, the relationship between vitamin D status and inflammation has not been previously investigated in cats. The aim of this study was to examine the relationship between serum 25(OH)D concentrations and leukocyte counts in hospitalised sick cats. Methods: Serum 25(OH)D concentrations, and haematology profiles were measured in 170 consecutive hospitalised sick cats. A binary logistical regression model examined the relationship between serum 25(OH)D concentration, age, sex, breed and neutrophil, monocyte, eosinophil and lymphocyte counts.Results: Cats with a neutrophilia had lower serum 25(OH)D concentrations than cats with neutrophil concentrations below the upper limit of the reference range. There were no differences in serum 25(OH)D concentrations in cats with monocyte, lymphocyte or eosinophil counts above their respective reference interval compared to cats with counts below the upper limit of the reference interval. Conclusions and relevance: Hospitalised cats with a neutrophil count above the reference range had lower vitamin D status. There is a need to establish whether lower vitamin D status is a cause or consequence of increased neutrophil counts.IntroductionThe actions of vitamin D have been classically understood in terms of its role in regulating calcium homeostasis and bone metabolism. However, more diverse physiological roles of vitamin D have been demonstrated in recent years and numerous cell types have been shown to express the vitamin D receptor. ADDIN EN.CITE <EndNote><Cite><Year>2012</Year><RecNum>1</RecNum><DisplayText>[1, 2]</DisplayText><record><rec-number>1</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869625">1</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors></contributors><titles><title>The Nonskeletal Effects of Vitamin D: An Endocrine Society Scientific Statement</title><secondary-title>Endocrine Reviews</secondary-title></titles><periodical><full-title>Endocrine Reviews</full-title></periodical><pages>456-492</pages><volume>33</volume><number>3</number><dates><year>2012</year></dates><accession-num>22596255</accession-num><urls><related-urls><url> app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869625">2</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Christakos, Sylvia</author><author>Dhawan, Puneet</author><author>Liu, Yan</author><author>Peng, Xiaorong</author><author>Porta, Angela</author></authors></contributors><titles><title>New insights into the mechanisms of vitamin D action</title><secondary-title>Journal of Cellular Biochemistry</secondary-title></titles><periodical><full-title>Journal of Cellular Biochemistry</full-title></periodical><pages>695-705</pages><volume>88</volume><number>4</number><dates><year>2003</year></dates><isbn>1097-4644</isbn><urls></urls></record></Cite></EndNote>[1, 2] Low serum vitamin D status, most commonly assessed by measuring serum 25-hydroxvitamin D (25(OH)D) concentrations, are commonly reported in a number of human and canine diseases including hypertension ADDIN EN.CITE <EndNote><Cite><Author>Tamez</Author><Year>2012</Year><RecNum>3</RecNum><DisplayText>[3]</DisplayText><record><rec-number>3</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869625">3</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tamez, Hector</author><author>Thadhani, Ravi I</author></authors></contributors><titles><title>Vitamin D and hypertension: an update and review</title><secondary-title>Current Opinion in Nephrology and Hypertension</secondary-title></titles><periodical><full-title>Current Opinion in Nephrology and Hypertension</full-title></periodical><pages>492-499</pages><volume>21</volume><number>5</number><dates><year>2012</year></dates><isbn>1062-4821</isbn><urls></urls></record></Cite></EndNote>[3], diabetes mellitus, ADDIN EN.CITE <EndNote><Cite><Author>Feng</Author><Year>2015</Year><RecNum>76</RecNum><DisplayText>[4]</DisplayText><record><rec-number>76</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1446981677">76</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Feng, R.</author><author>Li, Y.</author><author>Li, G.</author><author>Li, Z.</author><author>Zhang, Y.</author><author>Li, Q.</author><author>Sun, C.</author></authors></contributors><auth-address>Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, China; National Key Discipline, Harbin Medical University, Harbin, China.
Dean Office, Harbin Medical University, Harbin, China.
Department of Endocrinology, Second Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: liqiang_hmu@.
Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, China; National Key Discipline, Harbin Medical University, Harbin, China. Electronic address: changhao2002sun@.</auth-address><titles><title>Lower serum 25 (OH) D concentrations in type 1 diabetes: A meta-analysis</title><secondary-title>Diabetes Res Clin Pract</secondary-title></titles><periodical><full-title>Diabetes Res Clin Pract</full-title></periodical><pages>e71-5</pages><volume>108</volume><number>3</number><edition>2015/04/04</edition><keywords><keyword>Meta-analysis</keyword><keyword>Serum vitamin D</keyword><keyword>Type 1 diabetes</keyword></keywords><dates><year>2015</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>1872-8227 (Electronic)
0168-8227 (Linking)</isbn><accession-num>25836943</accession-num><urls></urls><electronic-resource-num>10.1016/j.diabres.2014.12.008</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[4] cardiovascular disease, PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HcmFuZGk8L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA [7, 8] autoimmune conditions ADDIN EN.CITE <EndNote><Cite><Author>Kriegel</Author><Year>2011</Year><RecNum>9</RecNum><DisplayText>[9]</DisplayText><record><rec-number>9</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869625">9</key></foreign-keys><ref-type name="Conference Proceedings">10</ref-type><contributors><authors><author>Kriegel, Martin A</author><author>Manson, JoAnn E</author><author>Costenbader, Karen H</author></authors></contributors><titles><title>Does vitamin D affect risk of developing autoimmune disease?: a systematic review</title><secondary-title>Seminars in arthritis and rheumatism</secondary-title></titles><pages>512-531. e8</pages><volume>40</volume><number>6</number><dates><year>2011</year></dates><publisher>Elsevier</publisher><isbn>0049-0172</isbn><urls></urls></record></Cite></EndNote>[9], chronic enteropathies PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NZWxsYW5ieTwvQXV0aG9yPjxZZWFyPjIwMDU8L1llYXI+
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ADDIN EN.CITE.DATA [12-16] In feline medicine low vitamin D status has been observed in cats with mycobacterial infections ADDIN EN.CITE <EndNote><Cite><Author>Lalor</Author><Year>2012</Year><RecNum>15</RecNum><DisplayText>[15]</DisplayText><record><rec-number>15</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869626">15</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lalor, S. M.</author><author>Mellanby, R. J.</author><author>Friend, E. J.</author><author>Bowlt, K. L.</author><author>Berry, J.</author><author>Gunn-Moore, D.</author></authors></contributors><auth-address>Division of Clinical Veterinary Sciences, The Royal (Dick) School of Veterinary Studies, Easter Bush Veterinary Centre, University of Edinburgh, Roslin, Edinburgh, UK. slalor@staffmail.ed.ac.uk</auth-address><titles><title>Domesticated cats with active mycobacteria infections have low serum vitamin D (25(OH)D) concentrations</title><secondary-title>Transboundary and Emerging Diseases</secondary-title><alt-title>Transboundary and Emerging Diseases</alt-title></titles><periodical><full-title>Transboundary and Emerging Diseases</full-title><abbr-1>Transboundary and Emerging Diseases</abbr-1></periodical><alt-periodical><full-title>Transboundary and Emerging Diseases</full-title><abbr-1>Transboundary and Emerging Diseases</abbr-1></alt-periodical><pages>279-81</pages><volume>59</volume><number>3</number><edition>2011/10/18</edition><keywords><keyword>Animals</keyword><keyword>Cat Diseases/*blood</keyword><keyword>Cats</keyword><keyword>Mycobacterium Infections/blood/*veterinary</keyword><keyword>Vitamin D/*analogs & derivatives/blood</keyword></keywords><dates><year>2012</year><pub-dates><date>Jun</date></pub-dates></dates><accession-num>21999899</accession-num><urls></urls><electronic-resource-num>10.1111/j.1865-1682.2011.01265.x</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[15] and in cats with inflammatory bowel disease or small cell gastrointestinal lymphoma. ADDIN EN.CITE <EndNote><Cite><Author>Lalor</Author><Year>2014</Year><RecNum>17</RecNum><DisplayText>[17]</DisplayText><record><rec-number>17</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869626">17</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lalor, S.</author><author>Schwartz, A. M.</author><author>Titmarsh, H.</author><author>Reed, N.</author><author>Tasker, S.</author><author>Boland, L.</author><author>Berry, J.</author><author>Gunn-Moore, D.</author><author>Mellanby, R. J.</author></authors></contributors><titles><title>Cats with Inflammatory Bowel Disease and Intestinal Small Cell Lymphoma Have Low Serum Concentrations of 25-Hydroxyvitamin D</title><secondary-title>Journal of Veterinary Internal Medicine</secondary-title><alt-title>Journal of Veterinary Internal Medicine</alt-title></titles><periodical><full-title>Journal of Veterinary Internal Medicine</full-title></periodical><alt-periodical><full-title>Journal of Veterinary Internal Medicine</full-title></alt-periodical><pages>351-355</pages><volume>28</volume><number>2</number><keywords><keyword>Small cell lymphoma</keyword><keyword>Inflammatory bowel disease</keyword><keyword>Vitamin D</keyword><keyword>Calcium</keyword></keywords><dates><year>2014</year></dates><isbn>1939-1676</isbn><urls><related-urls><url>;[17] Importantly, serum 25(OH)D concentrations are also predictive of short-term mortality in hospitalised cats. ADDIN EN.CITE <EndNote><Cite><Author>Titmarsh</Author><Year>2015</Year><RecNum>18</RecNum><DisplayText>[18]</DisplayText><record><rec-number>18</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869626">18</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Titmarsh, Helen</author><author>Kilpatrick, Scott</author><author>Sinclair, Jennifer</author><author>Boag, Alisdair</author><author>Bode, Elizabeth F.</author><author>Lalor, Stephanie M.</author><author>Gaylor, Donna</author><author>Berry, Jacqueline</author><author>Bommer, Nicholas X.</author><author>Gunn-Moore, Danielle</author><author>Reed, Nikki</author><author>Handel, Ian</author><author>Mellanby, Richard J.</author></authors></contributors><titles><title>Vitamin D Status Predicts 30 Day Mortality in Hospitalised Cats</title><secondary-title>PLoS ONE</secondary-title></titles><periodical><full-title>PLoS One</full-title></periodical><pages>e0125997</pages><volume>10</volume><number>5</number><dates><year>2015</year><pub-dates><date>05/13
02/01/received
03/27/accepted</date></pub-dates></dates><pub-location>San Francisco, CA USA</pub-location><publisher>Public Library of Science</publisher><isbn>1932-6203</isbn><accession-num>PMC4430519</accession-num><urls><related-urls><url>;[18] Similarly, low serum 25(OH)D concentrations have also been found to be predictive of mortality in people PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NZWxhbWVkPC9BdXRob3I+PFllYXI+MjAwODwvWWVhcj48
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ADDIN EN.CITE.DATA [22-28] In humans serum 25(OH)D concentrations have been inversely associated with markers of inflammation including acute phase proteins and, pro-inflammatory cytokines. This has been demonstrated in a number of diseases including inflammatory polyarthritis, ADDIN EN.CITE <EndNote><Cite><Author>Patel</Author><Year>2007</Year><RecNum>29</RecNum><DisplayText>[29]</DisplayText><record><rec-number>29</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869627">29</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Patel, S.</author><author>Farragher, T.</author><author>Berry, J.</author><author>Bunn, D.</author><author>Silman, A.</author><author>Symmons, D.</author></authors></contributors><auth-address>St. Helier University Hospital, Carshalton, London, UK. sanjeev.patel@epsom-sthelier.nhs.uk</auth-address><titles><title>Association between serum vitamin D metabolite levels and disease activity in patients with early inflammatory polyarthritis</title><secondary-title>Arthritis and Rheumatology</secondary-title></titles><periodical><full-title>Arthritis and Rheumatology</full-title></periodical><pages>2143-9</pages><volume>56</volume><number>7</number><edition>2007/06/30</edition><keywords><keyword>Antirheumatic Agents/therapeutic use</keyword><keyword>Arthritis/ blood/drug therapy/physiopathology</keyword><keyword>Biological Markers/blood</keyword><keyword>Calcifediol/ blood</keyword><keyword>Calcitriol/ blood</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Inflammation</keyword><keyword>Joints/physiopathology</keyword><keyword>Male</keyword><keyword>Patient Selection</keyword></keywords><dates><year>2007</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0004-3591 (Print)
0004-3591 (Linking)</isbn><accession-num>17599737</accession-num><urls></urls><electronic-resource-num>10.1002/art.22722</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[29] diabetes mellitus, ADDIN EN.CITE <EndNote><Cite><Author>Shih</Author><Year>2014</Year><RecNum>30</RecNum><DisplayText>[30]</DisplayText><record><rec-number>30</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869627">30</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Shih, E. M.</author><author>Mittelman, S.</author><author>Pitukcheewanont, P.</author><author>Azen, C. G.</author><author>Monzavi, R.</author></authors></contributors><auth-address>Center for Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles, Los Angeles, CA, 90027, USA.</auth-address><titles><title>Effects of vitamin D repletion on glycemic control and inflammatory cytokines in adolescents with type 1 diabetes</title><secondary-title>Pediatric Diabetes</secondary-title><alt-title>Pediatric diabetes</alt-title></titles><periodical><full-title>Pediatric Diabetes</full-title><abbr-1>Pediatric diabetes</abbr-1></periodical><alt-periodical><full-title>Pediatric Diabetes</full-title><abbr-1>Pediatric diabetes</abbr-1></alt-periodical><edition>2014/12/20</edition><keywords><keyword>adolescents</keyword><keyword>inflammatory cytokines</keyword><keyword>microvascular complications</keyword><keyword>type 1 diabetes</keyword><keyword>vitamin D</keyword></keywords><dates><year>2014</year><pub-dates><date>Dec 18</date></pub-dates></dates><isbn>1399-543x</isbn><accession-num>25524404</accession-num><urls></urls><electronic-resource-num>10.1111/pedi.12238</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>Eng</language></record></Cite></EndNote>[30] autoimmune diseases,PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5kZSBTb3V6YTwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+
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ADDIN EN.CITE.DATA [33, 34] and human immunodeficiency virus. ADDIN EN.CITE <EndNote><Cite><Author>Poudel-Tandukar</Author><Year>2013</Year><RecNum>35</RecNum><DisplayText>[35]</DisplayText><record><rec-number>35</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869628">35</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Poudel-Tandukar, K.</author><author>Poudel, K. C.</author><author>Jimba, M.</author><author>Kobayashi, J.</author><author>Johnson, C. A.</author><author>Palmer, P. H.</author></authors></contributors><auth-address>Waseda Institute for Advanced Study, Waseda University, Tokyo, Japan.</auth-address><titles><title>Serum 25-hydroxyvitamin d levels and C-reactive protein in persons with human immunodeficiency virus infection</title><secondary-title>AIDS Research And Human Retroviruses</secondary-title></titles><periodical><full-title>AIDS Research And Human Retroviruses</full-title></periodical><pages>528-34</pages><volume>29</volume><number>3</number><edition>2012/09/26</edition><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>C-Reactive Protein/ analysis</keyword><keyword>Cross-Sectional Studies</keyword><keyword>Female</keyword><keyword>HIV/ pathogenicity</keyword><keyword>HIV Infections/ pathology</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Nepal</keyword><keyword>Serum/chemistry</keyword><keyword>Sex Factors</keyword><keyword>Vitamin D/ analogs & derivatives/blood</keyword><keyword>Young Adult</keyword></keywords><dates><year>2013</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1931-8405 (Electronic)
0889-2229 (Linking)</isbn><accession-num>23003113</accession-num><urls></urls><custom2>PMC3581068</custom2><electronic-resource-num>10.1089/aid.2012.0120</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[35] Inflammatory markers are also increased in elderly and healthy people with low serum concentrations of vitamin D.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EZSBWaXRhPC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48
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ADDIN EN.CITE.DATA [36-38] In addition, low vitamin D status has been associated with markers of inflammation in dogs with haemoabdomens ADDIN EN.CITE <EndNote><Cite><Author>Selting</Author><Year>2014</Year><RecNum>8</RecNum><DisplayText>[8]</DisplayText><record><rec-number>8</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869625">8</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Selting, K. A.</author><author>Sharp, C. R.</author><author>Ringold, R.</author><author>Thamm, D. H.</author><author>Backus, R.</author></authors></contributors><titles><title>Serum 25-hydroxyvitamin D concentrations in dogs – correlation with health and cancer risk</title><secondary-title>Veterinary and Comparative Oncology</secondary-title></titles><periodical><full-title>Veterinary and Comparative Oncology</full-title></periodical><pages>n/a-n/a</pages><keywords><keyword>biomarker</keyword><keyword>calcium</keyword><keyword>C-reactive protein</keyword><keyword>diet</keyword><keyword>inflammation</keyword><keyword>nutrition</keyword></keywords><dates><year>2014</year></dates><publisher>Blackwell Publishing Ltd</publisher><isbn>1476-5829</isbn><urls><related-urls><url>;[8] and dogs with chronic enteropathies. ADDIN EN.CITE <EndNote><Cite><Author>Titmarsh</Author><Year>2015</Year><RecNum>41</RecNum><DisplayText>[39]</DisplayText><record><rec-number>41</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869629">41</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Titmarsh, Helen F.</author><author>Gow, Adam G.</author><author>Kilpatrick, Scott</author><author>Cartwright, Jennifer A.</author><author>Milne, Elspeth M.</author><author>Philbey, Adrian W.</author><author>Berry, Jacqueline</author><author>Handel, Ian</author><author>Mellanby, Richard J.</author></authors></contributors><titles><title>Low Vitamin D Status Is Associated with Systemic and Gastrointestinal Inflammation in Dogs with a Chronic Enteropathy</title><secondary-title>PLoS ONE</secondary-title></titles><periodical><full-title>PLoS One</full-title></periodical><pages>e0137377</pages><volume>10</volume><number>9</number><dates><year>2015</year></dates><publisher>Public Library of Science</publisher><urls><related-urls><url>;[39]Despite a number of studies having investigated the association between serum 25(OH)D concentrations and inflammation, surprisingly few studies have looked at the relationship between serum vitamin D concentrations and leukocyte populations in either human or veterinary patients. ADDIN EN.CITE <EndNote><Cite><Author>Mellenthin</Author><Year>2014</Year><RecNum>39</RecNum><DisplayText>[40]</DisplayText><record><rec-number>39</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869628">39</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mellenthin, Liesa</author><author>Wallaschofski, Henri</author><author>Grotevendt, Anne</author><author>V?lzke, Henry</author><author>Nauck, Matthias</author><author>Hannemann, Anke</author></authors></contributors><titles><title>Association between serum vitamin D concentrations and inflammatory markers in the general adult population</title><secondary-title>Metabolism</secondary-title></titles><periodical><full-title>Metabolism</full-title></periodical><pages>1056-1062</pages><volume>63</volume><number>8</number><keywords><keyword>Epidemiology</keyword><keyword>Inflammation</keyword><keyword>C-reactive protein</keyword><keyword>Fibrinogen</keyword><keyword>White blood cell count</keyword></keywords><dates><year>2014</year><pub-dates><date>8//</date></pub-dates></dates><isbn>0026-0495</isbn><urls><related-urls><url>;[40] One study which investigated the association between white blood cell concentrations and serum 25(OH)D found an inverse relationship between these two parameters in smokers. ADDIN EN.CITE <EndNote><Cite><Author>Mellenthin</Author><Year>2014</Year><RecNum>39</RecNum><DisplayText>[40]</DisplayText><record><rec-number>39</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869628">39</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mellenthin, Liesa</author><author>Wallaschofski, Henri</author><author>Grotevendt, Anne</author><author>V?lzke, Henry</author><author>Nauck, Matthias</author><author>Hannemann, Anke</author></authors></contributors><titles><title>Association between serum vitamin D concentrations and inflammatory markers in the general adult population</title><secondary-title>Metabolism</secondary-title></titles><periodical><full-title>Metabolism</full-title></periodical><pages>1056-1062</pages><volume>63</volume><number>8</number><keywords><keyword>Epidemiology</keyword><keyword>Inflammation</keyword><keyword>C-reactive protein</keyword><keyword>Fibrinogen</keyword><keyword>White blood cell count</keyword></keywords><dates><year>2014</year><pub-dates><date>8//</date></pub-dates></dates><isbn>0026-0495</isbn><urls><related-urls><url>;[40] The lack of studies which have examined the relationship between leukocytes and vitamin D status in humans resulted in Lee et al (2015) concluding that ‘evaluation of different forms of inflammatory cells, not just total white blood cell count, may be a useful method to identify the association of vitamin D and inflammation’ ADDIN EN.CITE <EndNote><Cite><Author>Lee</Author><Year>2015</Year><RecNum>40</RecNum><DisplayText>[41]</DisplayText><record><rec-number>40</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869628">40</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lee, H.</author><author>Kim, K. N.</author><author>Lim, Y. H.</author><author>Hong, Y. C.</author></authors></contributors><auth-address>Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
Environmental Health Center, Seoul National University College of Medicine, Seoul, Korea ; Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Korea.
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea ; Environmental Health Center, Seoul National University College of Medicine, Seoul, Korea ; Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Korea.</auth-address><titles><title>Interaction of Vitamin D and Smoking on Inflammatory Markers in the Urban Elderly</title><secondary-title>J Prev Med Public Health</secondary-title></titles><periodical><full-title>J Prev Med Public Health</full-title></periodical><pages>249-56</pages><volume>48</volume><number>5</number><edition>2015/10/03</edition><keywords><keyword>25-Hydroxyvitamin D2</keyword><keyword>C-reactive protein</keyword><keyword>Inflammation</keyword><keyword>Leukocytes</keyword><keyword>Smoking</keyword><keyword>Vitamin D</keyword></keywords><dates><year>2015</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>2233-4521 (Electronic)
1975-8375 (Linking)</isbn><accession-num>26429291</accession-num><urls></urls><custom2>PMC4592026</custom2><electronic-resource-num>10.3961/jpmph.15.042</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[41]. Despite the growing body of work investigating the relationship between serum 25(OH)D concentrations and illness in humans and dogs, the association between 25(OH)D and inflammation has not been previously investigated in cats. Therefore, the objective of this study was to measure serum concentrations of 25(OH)D, alongside whole blood neutrophil, lymphocyte, monocyte and eosinophil numbers in a population of hospitalised sick cats. The hypothesis of the study was that there would be a negative relationship between serum 25(OH)D concentrations and leukocyte counts. Material and MethodsCats consecutively examined at the Hospital for Small Animals, Royal Dick School of Veterinary Studies, were considered for inclusion in the study. Clinical records were reviewed for each cat enrolled. The age, sex, breed and final diagnosis was recorded for each cat. In order to be eligible for inclusion the following clinical data needed to be available; total white blood cell count, segmented and band neutrophil, monocyte, eosinophil and lymphocyte counts. In addition residual stored serum samples had to be available for 25(OH)D quantification.Following handling of blood samples for routine diagnostic procedures on the day of admission, serum samples were initally stored at -20°C and later moved to -80oC for longer term storage until 25(OH)D concentrations were measured in batches. Vitamin D is extremely stable even when stored at -20oC. ADDIN EN.CITE <EndNote><Cite><Author>Wielders</Author><Year>2009</Year><RecNum>42</RecNum><DisplayText>[42]</DisplayText><record><rec-number>42</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869629">42</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wielders, Jos P. M.</author><author>Wijnberg, Ferdinand A.</author></authors></contributors><titles><title>Preanalytical Stability of 25(OH)–Vitamin D3 in Human Blood or Serum at Room Temperature: Solid as a Rock</title><secondary-title>Clinical Chemistry</secondary-title></titles><periodical><full-title>Clinical Chemistry</full-title></periodical><pages>1584-1585</pages><volume>55</volume><number>8</number><dates><year>2009</year><pub-dates><date>August 1, 2009</date></pub-dates></dates><urls><related-urls><url>;[42] Serum concentrations of 25(OH)D2 and 25(OH)D3 were determined by liquid chromatography tandem mass spectrophotometry (LC-MS/MS) using an ABSciex 5500 tandem mass spectrophotometer (Warrington, UK) and the Chromsystems (Munich, Germany) 25OHD kit for LC-MS/MS following the manufacturers’ instructions (intra- and inter-assay CV 3.7% and 4.8% respectively). This Supraregional Assay Service laboratory is accredited by CPA UK (CPA number 0865) and has been certified as proficient by the international Vitamin D Quality Assurance Scheme (DEQAS). Total 25(OH)D is defined as the sum of 25(OH)D2 and 25(OH)D3. Haematology variables were measured on an ADVIA(r) 2120i System with Autoslide (Siemens Medical Solutions Diagnostics Ltd California, USA). A manual white blood cell differential count was undertaken on at least 100 leukocytes to establish the concentrations of neutrophils, monocytes, lymphocytes, eosinophils and basophils. Blood smears from all cases were evaluated under the direct supervision of a Board-certified veterinary clinical pathologist. Total calcium concentrations were measured using an ILab650 biochemistry analyser (Diamond Diagnostics, USA).The relationship between serum 25(OH)D concentrations and neutrophils, lymphocytes, monocytes and eosinophils was initially examined using dot plots which plotted leukocyte counts against serum 25(OH)D concentrations. The relationship between 25(OH)D concentrations in segmented neutrophils, lymphocytes, monocytes and eosinophils populations which were above or below the upper limit of the reference interval were examined using a Mann Whitney U test. In the four leukocyte populations, the relationship between 25(OH)D concentrations, age, breed and sex was investigated by a binary logistical regression model. Co-variates were removed from the initial model to minimise Akaike Information Criterion (AIC), a parameter penalised measure of best fit, to give a final parsimonious model. The relationship between calcium and serum 25(OH)D concentrations was assessed by Spearman’s rank correlation test. ?The study was approved by the University of Edinburgh’s Veterinary Ethical Review Committee. Informed consent for the storage and subsequent use of residual clinical blood samples for research purposes was obtained at admission for each cat enrolled.Results?One hundred and seventy cats were included in the study. The median age of the cats was 108 months (2.5-264 months). There were 4 entire males, 102 neutered males, 1 entire female and 63 neutered female cats. Breeds included in the study were 110 Domestic Short Hair cats, 15 Domestic Long Hair cats, 8 Maine Coons, 3 Oriental Short Hairs, 8 Burmese, 7 Bengals, 6 Siamese, 2 Ragdolls and one of each of the following breeds; Chinchilla, Abyssinian, Persian, British Blue, Manx, Siberian, Russian Blue, Egyptian, Norwegian Forest Cat, Burmilla and Tonkinese. There was a significant positive correlation between total calcium and 25(OH)D concentration (r=0.21, p<0.01).Dot plots of serum 25(OH)D concentrations from cats with haematology parameters above or below the upper reference interval are shown in figure 1. Serum 25(OH)D concentrations were significantly lower in cats with a segmented neutrophil count above the upper reference interval compared to cats with a segmented neutrophil count below the upper reference range (p=0.04). This significant difference remained even after removal of the high outlying result in the <12.8x109/l group. Twelve cats had band neutrophils. The median serum concentration of 25(OH)D from cats with band neutrophils was 59.8nmol/l compared to cats with band neutrophils was 97.4nmol/l. This difference approached significance (p=0.06). There was no significant difference in 25(OH)D concentrations in cats with eosinophil, lymphocyte and monocyte counts above upper reference interval compared to cats with leukocyte counts below the upper end of the reference interval. The lower serum 25(OH)D concentrations observed in cats with a segmented neutrophil count above the upper reference interval was not confounded by age, breed or sex as the final logistic regression model only included 25(OH)D concentrations as a predictor of increased neutrophil counts (p=0.021). The odds of having a neutrophil count within the reference interval increased by 1.32 (1.04-1.72 95% CI) per 25nmol/l increase in serum concentrations of 25(OH)D. Discussion The main finding of this study was that cats with a neutrophilia have lower vitamin D status than cats with neutrophil counts below the upper reference interval. This observation is consistent with studies in human and canine patients together with experimental models of inflammation. For example, a study of over 1300 children found a negative correlation between neutrophil count and 25(OH)D concentrations. ADDIN EN.CITE <EndNote><Cite><Author>Hollams</Author><Year>2011</Year><RecNum>43</RecNum><DisplayText>[43]</DisplayText><record><rec-number>43</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869629">43</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hollams, E.M.</author><author>Hart, P.H.</author><author>Holt, B.J.</author><author>Serralha, M.</author><author>Parsons, F.</author><author>de Klerk, N.H.</author><author>Zhang, G.</author><author>Sly, P.D.</author><author>Holt, P.G.</author></authors></contributors><titles><title>Vitamin D and atopy and asthma phenotypes in children: a longitudinal cohort study</title><secondary-title>European Respiratory Journal</secondary-title></titles><periodical><full-title>European Respiratory Journal</full-title></periodical><pages>1320-1327</pages><volume>38</volume><number>6</number><dates><year>2011</year><pub-dates><date>December 1, 2011</date></pub-dates></dates><urls><related-urls><url>;[43] Furthermore, vitamin D supplementation has been shown to reduce the proportion of neutrophils in a murine model of allergic airway disease. ADDIN EN.CITE <EndNote><Cite><Author>Gorman</Author><Year>2013</Year><RecNum>44</RecNum><DisplayText>[44]</DisplayText><record><rec-number>44</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869629">44</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gorman, Shelley</author><author>Weeden, Clare E.</author><author>Tan, Daryl H. W.</author><author>Scott, Naomi M.</author><author>Hart, Julie</author><author>Foong, Rachel E.</author><author>Mok, Danny</author><author>Stephens, Nahiid</author><author>Zosky, Graeme</author><author>Hart, Prue H.</author></authors></contributors><titles><title>Reversible Control by Vitamin D of Granulocytes and Bacteria in the Lungs of Mice: An Ovalbumin-Induced Model of Allergic Airway Disease</title><secondary-title>PLoS ONE</secondary-title></titles><periodical><full-title>PLoS One</full-title></periodical><pages>e67823</pages><volume>8</volume><number>6</number><dates><year>2013</year><pub-dates><date>06/24
01/25/received
05/21/accepted</date></pub-dates></dates><pub-location>San Francisco, USA</pub-location><publisher>Public Library of Science</publisher><isbn>1932-6203</isbn><accession-num>PMC3691156</accession-num><urls><related-urls><url>;[44] The finding of a negative relationship between 25(OH)D concentrations and segmented neutrophils is also consistent with our recent work in dogs with intestinal inflammation. ADDIN EN.CITE <EndNote><Cite><Author>Titmarsh</Author><Year>2015</Year><RecNum>41</RecNum><DisplayText>[39]</DisplayText><record><rec-number>41</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869629">41</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Titmarsh, Helen F.</author><author>Gow, Adam G.</author><author>Kilpatrick, Scott</author><author>Cartwright, Jennifer A.</author><author>Milne, Elspeth M.</author><author>Philbey, Adrian W.</author><author>Berry, Jacqueline</author><author>Handel, Ian</author><author>Mellanby, Richard J.</author></authors></contributors><titles><title>Low Vitamin D Status Is Associated with Systemic and Gastrointestinal Inflammation in Dogs with a Chronic Enteropathy</title><secondary-title>PLoS ONE</secondary-title></titles><periodical><full-title>PLoS One</full-title></periodical><pages>e0137377</pages><volume>10</volume><number>9</number><dates><year>2015</year></dates><publisher>Public Library of Science</publisher><urls><related-urls><url>;[39]This study demonstrated that vitamin D status was negatively correlated with neutrophil counts, together with several other markers of systemic and intestinal inflammation, in dogs with a chronic enteropathy. It is presently unclear if low 25(OH)D concentrations are a cause or consequence of inflammation. It has been hypothesised that serum 25(OH)D may act as a negative acute phase protein.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XYWxkcm9uPC9BdXRob3I+PFllYXI+MjAxMzwvWWVhcj48
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ADDIN EN.CITE.DATA [46, 47] Decreases in serum 25(OH)D concentrations have also been reported with spontaneously occurring inflammatory conditions such as acute pancreatitis. ADDIN EN.CITE <EndNote><Cite><Author>Bang</Author><Year>2011</Year><RecNum>48</RecNum><DisplayText>[48]</DisplayText><record><rec-number>48</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869629">48</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bang, Ulrich C.</author><author>Novovic, Srdan</author><author>Andersen, Anders M?ller</author><author>Fenger, Mogens</author><author>Hansen, Mark Berner</author><author>Jensen, Jens-Erik Beck</author></authors></contributors><titles><title>Variations in Serum 25-Hydroxyvitamin D during Acute Pancreatitis: An Exploratory Longitudinal Study</title><secondary-title>Endocrine Research</secondary-title></titles><periodical><full-title>Endocrine Research</full-title></periodical><pages>135-141</pages><volume>36</volume><number>4</number><dates><year>2011</year></dates><accession-num>21973232</accession-num><urls><related-urls><url>;[48] Alterations in vitamin D status may also occur due the effect of inflammation on vitamin D binding proteins. For example, serum concentrations of vitamin D binding protein concentration decrease in acute inflammation.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XYWxkcm9uPC9BdXRob3I+PFllYXI+MjAxMzwvWWVhcj48
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ADDIN EN.CITE.DATA [45] In contrast, other investigators have demonstrated that patients with lower 25(OH)D concentrations are more likely to develop an inflammatory response following immune stimulation. For example, the acute phase response following administration of parenteral bisphosphonates was greater in patients with low vitamin D status, suggesting that hypovitaminosis D may predispose people to acute inflammatory reactions. ADDIN EN.CITE <EndNote><Cite><Author>Bertoldo</Author><Year>2010</Year><RecNum>50</RecNum><DisplayText>[49]</DisplayText><record><rec-number>50</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869629">50</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bertoldo, Francesco</author><author>Pancheri, Serena</author><author>Zenari, Sonia</author><author>Boldini, Stefania</author><author>Giovanazzi, Benedetta</author><author>Zanatta, Mirko</author><author>Valenti, Maria Teresa</author><author>Carbonare, Luca Dalle</author><author>Cascio, Vincenzo Lo</author></authors></contributors><titles><title>Serum 25-hydroxyvitamin D levels modulate the acute-phase response associated with the first nitrogen-containing bisphosphonate infusion</title><secondary-title>Journal of Bone and Mineral Research</secondary-title></titles><periodical><full-title>Journal of Bone and Mineral Research</full-title></periodical><pages>447-454</pages><volume>25</volume><number>3</number><keywords><keyword>vitamin D</keyword><keyword>acute-phase response</keyword><keyword>amino-bisphosphonates</keyword><keyword>zoledronic acid</keyword><keyword>flu-like syndrome</keyword></keywords><dates><year>2010</year></dates><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><isbn>1523-4681</isbn><urls><related-urls><url>;[49] In addition, other studies suggest that vitamin D may not decrease acutely in all inflammatory conditions. For example, no significant decreases in 25(OH)D concentrations were reported secondary to myocardial infarction. ADDIN EN.CITE <EndNote><Cite><Author>Barth</Author><Year>2012</Year><RecNum>52</RecNum><DisplayText>[50]</DisplayText><record><rec-number>52</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869629">52</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Barth, J H</author><author>Field, H P</author><author>Mather, A N</author><author>Plein, S</author></authors></contributors><titles><title>Serum 25 hydroxy-vitamin D does not exhibit an acute phase reaction after acute myocardial infarction</title><secondary-title>Annals of Clinical Biochemistry</secondary-title></titles><periodical><full-title>Annals of Clinical Biochemistry</full-title></periodical><pages>399-401</pages><volume>49</volume><number>4</number><dates><year>2012</year><pub-dates><date>July 1, 2012</date></pub-dates></dates><urls><related-urls><url>;[50] Similarly, there was no association between hypovitaminosis D and markers of an acute phase response in humans with pulmonary tuberculosis.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5GcmlpczwvQXV0aG9yPjxZZWFyPjIwMDg8L1llYXI+PFJl
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ADDIN EN.CITE.DATA [52], experimental models of colitis ADDIN EN.CITE <EndNote><Cite><Author>Laverny</Author><Year>2010</Year><RecNum>55</RecNum><DisplayText>[53]</DisplayText><record><rec-number>55</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869630">55</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Laverny, Gilles</author><author>Penna, Giuseppe</author><author>Vetrano, Stefania</author><author>Correale, Carmen</author><author>Nebuloni, Manuela</author><author>Danese, Silvio</author><author>Adorini, Luciano</author></authors></contributors><titles><title>Efficacy of a potent and safe vitamin D receptor agonist for the treatment of inflammatory bowel disease</title><secondary-title>Immunology Letters</secondary-title></titles><periodical><full-title>Immunology Letters</full-title></periodical><pages>49-58</pages><volume>131</volume><number>1</number><keywords><keyword>Inflammatory bowel disease</keyword><keyword>Vitamin D</keyword><keyword>VDR</keyword><keyword>TLR</keyword><keyword>Colitis</keyword><keyword>LPMC</keyword></keywords><dates><year>2010</year><pub-dates><date>6/15/</date></pub-dates></dates><isbn>0165-2478</isbn><urls><related-urls><url>;[53], models of cognitive dysfunction PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CcmlvbmVzPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48
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ADDIN EN.CITE.DATA [55] and interstitial cystitis ADDIN EN.CITE <EndNote><Cite><Author>Benigni</Author><Year>2006</Year><RecNum>58</RecNum><DisplayText>[56]</DisplayText><record><rec-number>58</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869630">58</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Benigni, F.</author><author>Baroni, E.</author><author>Zecevic, M.</author><author>Zvara, P.</author><author>Streng, T.</author><author>Hedlund, P.</author><author>Colli, E.</author><author>D'Ambrosio, D.</author><author>Andersson, K. E.</author></authors></contributors><auth-address>BioXell SpA, Milano, Italy. fabio.benigni@</auth-address><titles><title>Oral treatment with a vitamin D3 analogue (BXL628) has anti-inflammatory effects in rodent model of interstitial cystitis</title><secondary-title>BJU International</secondary-title></titles><periodical><full-title>BJU International</full-title></periodical><pages>617-24</pages><volume>97</volume><number>3</number><edition>2006/02/14</edition><keywords><keyword>Animals</keyword><keyword>Anti-Inflammatory Agents/*therapeutic use</keyword><keyword>Calcitriol/*analogs & derivatives/therapeutic use</keyword><keyword>Cholecalciferol/analogs & derivatives</keyword><keyword>Cystitis, Interstitial/*drug therapy/pathology</keyword><keyword>Female</keyword><keyword>Immunohistochemistry</keyword><keyword>Interleukin-13/metabolism</keyword><keyword>Mast Cells/metabolism</keyword><keyword>Mice</keyword><keyword>Mice, Inbred BALB C</keyword></keywords><dates><year>2006</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1464-4096 (Print)
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ADDIN EN.CITE.DATA [11] and in humans. ADDIN EN.CITE <EndNote><Cite><Author>Harris</Author><Year>2000</Year><RecNum>78</RecNum><DisplayText>[62]</DisplayText><record><rec-number>78</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1446996707">78</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Susan S. Harris</author><author>Elpidoforos Soteriades</author><author>Jo Anna Stina Coolidge</author><author>Sharmilla Mudgal</author><author>Bess Dawson-Hughes</author></authors></contributors><titles><title>Vitamin D Insufficiency and Hyperparathyroidism in a Low Income, Multiracial, Elderly Population</title><secondary-title>The Journal of Clinical Endocrinology & Metabolism</secondary-title></titles><periodical><full-title>The Journal of Clinical Endocrinology & Metabolism</full-title></periodical><pages>4125-4130</pages><volume>85</volume><number>11</number><dates><year>2000</year></dates><accession-num>11095443</accession-num><urls><related-urls><url>;[62] Our finding of an association between total calcium and 25(OH)D is consistent with the known effects of vitamin D, which includes increasing serum calcium concentrations by increasing dietary calcium absorption in the intestines, and acting in the kidney to promote calcium reabsorption and promote calcium resorption from bone. ADDIN EN.CITE <EndNote><Cite><Author>Gallieni</Author><Year>2009</Year><RecNum>73</RecNum><DisplayText>[63]</DisplayText><record><rec-number>73</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445939011">73</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gallieni, Maurizio</author><author>Cozzolino, Mario</author><author>Fallabrino, Giuditta</author><author>Pasho, Sabina</author><author>Olivi, Laura</author><author>Brancaccio, Diego</author></authors></contributors><titles><title>Vitamin D: physiology and pathophysiology</title><secondary-title>Int J Artif Organs</secondary-title></titles><periodical><full-title>Int J Artif Organs</full-title></periodical><pages>87-94</pages><volume>32</volume><number>2</number><dates><year>2009</year></dates><urls></urls></record></Cite></EndNote>[63] There are some limitations with this study. Firstly, leukocyte numbers can be altered by processes other than inflammation. For example, neutrophil numbers will transiently increase due to the release of adrenaline in response to stressful stimuli such as hospitalisation or blood sampling. Other limitations of this study include that cats come from a referral population. This makes it difficult to fully assess a number of confounding variables that could affect both serum vitamin D concentrations and leukocyte numbers. For example, the cats involved in this study may have been treated with a number of medications prior to admission to the hospital, which may have influenced haematological values. It is not known if medications influence serum 25(OH)D concentrations in cats. Although glucocorticoids may influence vitamin D concentrations in people, short term, anti-inflammatory doses of glucocorticoids do not significantly alter vitamin D metabolism in dogs. ADDIN EN.CITE <EndNote><Cite><Author>Kovalik</Author><Year>2012</Year><RecNum>49</RecNum><DisplayText>[64]</DisplayText><record><rec-number>49</rec-number><foreign-keys><key app="EN" db-id="vtazpxvdmveee5es0eaxv00hvs2tzpzf2ftr" timestamp="1444902655">49</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kovalik, M.</author><author>Thoday, K. L.</author><author>Evans, H.</author><author>Berry, J.</author><author>van den Broek, A. H. M.</author><author>Mellanby, R. J.</author></authors></contributors><titles><title>Short-term prednisolone therapy has minimal impact on calcium metabolism in dogs with atopic dermatitis</title><secondary-title>The Veterinary Journal</secondary-title></titles><periodical><full-title>The Veterinary Journal</full-title></periodical><pages>439-442</pages><volume>193</volume><number>2</number><keywords><keyword>Glucocorticoids</keyword><keyword>Parathyroid hormone</keyword><keyword>1,25-Dihydroxyvitamin D3</keyword><keyword>Calcium</keyword><keyword>Dog</keyword></keywords><dates><year>2012</year><pub-dates><date>8//</date></pub-dates></dates><isbn>1090-0233</isbn><urls><related-urls><url>;[64] As information regarding the influence of drugs on vitamin D homeostasis in cats is lacking, no cases were excluded based on previous medical therapy. However, it must be acknowledged that pre-treatment with drugs may have influenced the results of this study and future work investigating the effect of drugs such as steroids on serum 25(OH)D concentrations of cats would be valuable. Diet could also influence serum 25(OH)D in cats and a further limitation of this study is that the cats didn’t receive the same diets. However, it is standard practice in our hospital to record the diets fed to cats at the time of admission. All but one cat in this study was fed commercial cat food. As commercial cat foods are standardly supplemented with vitamin D within recommended limits, ADDIN EN.CITE <EndNote><Cite><Author>Federation</Author><Year>2014</Year><RecNum>69</RecNum><DisplayText>[65]</DisplayText><record><rec-number>69</rec-number><foreign-keys><key app="EN" db-id="zwted5afw5vdxnede995vzz4p2z5apdffesw" timestamp="1445869631">69</key></foreign-keys><ref-type name="Pamphlet">24</ref-type><contributors><authors><author>FEDIAF European Pet Food Industry Federation</author></authors><secondary-authors><author>FEDIAF European Pet Food Industry Federation</author></secondary-authors></contributors><titles><title>Nutritional Guidelines For Complete and Complementary Pet Food for Cats and Dogs</title></titles><dates><year>2014</year></dates><pub-location></pub-location><urls></urls></record></Cite></EndNote>[65] variation in vitamin D content of the diets consumed by cats enrolled in the study was unlikely to have been a significant confounding variableIn conclusion, the study has demonstrated that cats with a neutrophilia have lower vitamin D status than cats with a neutrophil count below the upper limit of the reference range. 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Digestive Diseases and Sciences, 2015.34.Garg, M., et al., Association of Circulating Vitamin D Concentrations with Intestinal but Not Systemic Inflammation in Inflammatory Bowel Disease. Inflammatory Bowel Diseases, 2013. 19(12): p. 2634-2643.35.Poudel-Tandukar, K., et al., Serum 25-hydroxyvitamin d levels and C-reactive protein in persons with human immunodeficiency virus infection. AIDS Research And Human Retroviruses, 2013. 29(3): p. 528-34.36.De Vita, F., et al., Relationship between vitamin D and inflammatory markers in older individuals. Age (Dordr), 2014. 36(4): p. 9694.37.Laird, E., et al., Vitamin D deficiency is associated with inflammation in older Irish adults. The Journal of Clinical Endocrinology and Metabolism2014. 99(5): p. 1807-15.38.Peterson, C.A. and M.E. Heffernan, Serum tumor necrosis factor-alpha concentrations are negatively correlated with serum 25(OH)D concentrations in healthy women. Journal of Inflammation 2008. 5: p. 10.39.Titmarsh, H.F., et al., Low Vitamin D Status Is Associated with Systemic and Gastrointestinal Inflammation in Dogs with a Chronic Enteropathy. PLoS ONE, 2015. 10(9): p. e0137377.40.Mellenthin, L., et al., Association between serum vitamin D concentrations and inflammatory markers in the general adult population. Metabolism, 2014. 63(8): p. 1056-1062.41.Lee, H., et al., Interaction of Vitamin D and Smoking on Inflammatory Markers in the Urban Elderly. J Prev Med Public Health, 2015. 48(5): p. 249-56.42.Wielders, J.P.M. and F.A. Wijnberg, Preanalytical Stability of 25(OH)–Vitamin D3 in Human Blood or Serum at Room Temperature: Solid as a Rock. Clinical Chemistry, 2009. 55(8): p. 1584-1585.43.Hollams, E.M., et al., Vitamin D and atopy and asthma phenotypes in children: a longitudinal cohort study. 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Immunology Letters, 2010. 131(1): p. 49-58.54.Briones, T.L. and H. Darwish, Vitamin D mitigates age-related cognitive decline through the modulation of pro-inflammatory state and decrease in amyloid burden. Journal of Neuroinflammation, 2012. 9: p. 244.55.Lee, J.W., et al., Renoprotective effect of paricalcitol via a modulation of the TLR4-NF-kappaB pathway in ischemia/reperfusion-induced acute kidney injury. Biochemical and Biophysical Research Communications 2014. 444(2): p. 121-7.56.Benigni, F., et al., Oral treatment with a vitamin D3 analogue (BXL628) has anti-inflammatory effects in rodent model of interstitial cystitis. BJU International, 2006. 97(3): p. 617-24.57.Abou-Raya, A., S. Abou-Raya, and M. Helmii, The effect of vitamin D supplementation on inflammatory and hemostatic markers and disease activity in patients with systemic lupus erythematosus: a randomized placebo-controlled trial. The Journal of rheumatology, 2013. 40(3): p. 265-72.58.Grossmann, R.E., et al., Impact of vitamin D supplementation on markers of inflammation in adults with cystic fibrosis hospitalized for a pulmonary exacerbation. European Journal of Clinical Nutrition2012. 66(9): p. 1072-4.59.Shab-Bidar, S., et al., Improvement of vitamin D status resulted in amelioration of biomarkers of systemic inflammation in the subjects with type 2 diabetes. Diabetes/metabolism research and reviews, 2012. 28(5): p. 424-30.60.Jorde, R., et al., No effect of supplementation with cholecalciferol on cytokines and markers of inflammation in overweight and obese subjects. Cytokine, 2010. 50(2): p. 175-180.61.Carlson, N., et al., Hypovitaminosis D correction and high-sensitivity C-reactive protein levels in hypertensive adults. The Permanente Journal, 2013. 17(4): p. 19-21.62.Harris, S.S., et al., Vitamin D Insufficiency and Hyperparathyroidism in a Low Income, Multiracial, Elderly Population. The Journal of Clinical Endocrinology & Metabolism, 2000. 85(11): p. 4125-4130.63.Gallieni, M., et al., Vitamin D: physiology and pathophysiology. Int J Artif Organs, 2009. 32(2): p. 87-94.64.Kovalik, M., et al., Short-term prednisolone therapy has minimal impact on calcium metabolism in dogs with atopic dermatitis. The Veterinary Journal, 2012. 193(2): p. 439-442.65.Federation, F.E.P.F.I., Nutritional Guidelines For Complete and Complementary Pet Food for Cats and Dogs, F.E.P.F.I. Federation, Editor. 2014: .FiguresFigure 1: Graphs showing 25(OH)D concentrations between cats with leukocytes numbers above and below upper limits of reference intervals ................
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