{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T02:07:11Z","timestamp":1775614031897,"version":"3.50.1"},"reference-count":80,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,4,28]],"date-time":"2024-04-28T00:00:00Z","timestamp":1714262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Midwestern University\u2019s One Health Research Stimulus Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>Human patients with type 1 diabetes mellitus (T1DM) are susceptible to several long-term complications that are related to glycemic control and immune dysregulation. Immune function remains relatively unexplored in dogs with naturally occurring diabetes mellitus (NODM). Calcitriol improves various aspects of immune function in a variety of species, but its effect in diabetic dogs remains unexplored. Therefore, the objectives of this study were to (i) evaluate immune function in dogs with NODM and determine if differences exist based on the level of clinical control and (ii) assess the immunomodulatory effects of calcitriol. Twenty diabetic dogs (clinically controlled, n = ten, not controlled, n = ten) and 20 non-diabetic, healthy control dogs were included in this prospective, case\u2013control study. Whole blood was incubated with calcitriol (10\u22127 M) or negative control, after which the samples were divided for phagocytosis and leukocyte cytokine response experiments. The phagocytosis of opsonized Escherichia coli (E. coli) was evaluated with flow cytometry. The samples for leukocyte cytokine response evaluations were stimulated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), or phosphate buffer solution (PBS; negative control), and tumor necrosis factor (TNF)-\u03b1, interleukin (IL)-6, IL-8, and IL-10 were measured in supernatant using a canine-specific multiplex bead-based assay. The leukocytes from diabetic dogs produced higher concentrations of IL-10 (p = 0.01), IL-6 (p &lt; 0.0001), and IL-8 (p &lt; 0.0001) than the control dogs while controlling for the intervention and stimulant. Calcitriol decreased the supernatant concentrations of TNF-\u03b1 (p &lt; 0.001) and IL-8 (p = 0.04) with concomitant increases in IL-6 (p = 0.005). Diabetic dogs had a lower percentage of leukocytes undergoing phagocytosis (p &lt; 0.0001) but a higher number of bacteria phagocytized per cell (p = 0.001) when compared to the control dogs. Calcitriol had no effect on phagocytic capacity. Lastly, the status of clinical control in diabetic dogs did not yield differences in immune function. These results support that dogs with NODM exhibit immune dysregulation and warrant additional investigation.<\/jats:p>","DOI":"10.3390\/vetsci11050193","type":"journal-article","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T06:13:22Z","timestamp":1714371202000},"page":"193","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Ex Vivo Immune Function and Modulatory Effects of Calcitriol in Dogs with Naturally Occurring Diabetes Mellitus"],"prefix":"10.3390","volume":"11","author":[{"given":"Jared A.","family":"Jaffey","sequence":"first","affiliation":[{"name":"Department of Specialty Medicine, Midwestern University, College of Veterinary Medicine, Glendale, AZ 85308, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachael","family":"Kreisler","sequence":"additional","affiliation":[{"name":"Department of Pathology and Population Medicine, Midwestern University, College of Veterinary Medicine, Glendale, AZ 85308, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas K.","family":"Graves","sequence":"additional","affiliation":[{"name":"Department of Specialty Medicine, Midwestern University, College of Veterinary Medicine, Glendale, AZ 85308, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9309-6213","authenticated-orcid":false,"given":"Layla","family":"Al-Nakkash","sequence":"additional","affiliation":[{"name":"Department of Physiology, Midwestern University, College of Graduate Studies, Glendale, AZ 85308, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert C.","family":"Backus","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Surgery, University of Missouri, College of Veterinary Medicine, Columbia, MO 65211, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren","family":"Allison","sequence":"additional","affiliation":[{"name":"Department of Specialty Medicine, Midwestern University, College of Veterinary Medicine, Glendale, AZ 85308, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.2460\/javma.2000.216.1414","article-title":"Breed distribution of dogs with diabetes mellitus admitted to a tertiary care facility","volume":"216","author":"Hess","year":"2000","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/S1090-0233(02)00242-3","article-title":"Time trends and risk factors for diabetes mellitus in dogs: Analysis of veterinary medical data base records (1970\u20131999)","volume":"165","author":"Guptill","year":"2003","journal-title":"Vet. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1023\/B:VERC.0000045441.77213.3b","article-title":"Breed distribution of canine diabetes mellitus in Italy","volume":"28","author":"Fracassi","year":"2004","journal-title":"Vet. Res. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1136\/vr.156.15.467","article-title":"Study of 253 dogs in the United Kingdom with diabetes mellitus","volume":"156","author":"Davison","year":"2005","journal-title":"Vet. Rec."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1111\/j.1939-1676.2007.tb01940.x","article-title":"Diabetes mellitus in a population of 180,000 insured dogs: Incidence, survival, and breed distribution","volume":"21","author":"Fall","year":"2007","journal-title":"J. Vet. Intern. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1007\/s00125-005-1921-1","article-title":"Canine diabetes mellitus: Can old dogs teach us new tricks?","volume":"48","author":"Catchpole","year":"2005","journal-title":"Diabetologia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e22","DOI":"10.1136\/vr.105467","article-title":"Epidemiological study of dogs with diabetes mellitus attending primary care veterinary clinics in Australia","volume":"187","author":"Yoon","year":"2020","journal-title":"Vet. Rec."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1002\/vms3.452","article-title":"Studying the heterogeneous pathogenesis of canine diabetes: Observational characterization of an island population","volume":"7","author":"Melian","year":"2021","journal-title":"Vet. Med. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1136\/vr.101950","article-title":"An epidemiological study of diabetes mellitus in dogs attending first opinion practice in the UK","volume":"174","author":"Mattin","year":"2014","journal-title":"Vet. Rec."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1002\/sctm.18-0163","article-title":"Concise Review: Canine Diabetes Mellitus as a Translational Model for Innovative Regenerative Medicine Approaches","volume":"8","author":"Moshref","year":"2019","journal-title":"Stem Cells Transl. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1111\/jvim.14357","article-title":"What\u2019s in a Name? Classification of Diabetes Mellitus in Veterinary Medicine and Why It Matters","volume":"30","author":"Gilor","year":"2016","journal-title":"J. Vet. Intern. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5326\/JAAHA-MS-6822","article-title":"2018 AAHA diabetes management guidelines for dogs and cats","volume":"54","author":"Behrend","year":"2018","journal-title":"J. Am. Anim. Hosp. Assoc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1111\/j.1365-2249.2006.03229.x","article-title":"Neutrophils and monocytes as potentially important sources of proinflammatory cytokines in diabetes","volume":"146","author":"Hatanaka","year":"2006","journal-title":"Clin. Exp. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1046\/j.1365-3083.1996.d01-43.x","article-title":"TNF production from peripheral blood mononuclear cells in diabetic patients after stimulation with alginate and lipopolysaccharide","volume":"43","author":"Kulseng","year":"1996","journal-title":"Scand. J. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1196\/annals.1375.027","article-title":"In vitro TNF-alpha and IL-6 production by adherent peripheral blood mononuclear cells obtained from type 1 and type 2 diabetic patients evaluated according to the metabolic control","volume":"1079","author":"Foss","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.2337\/diacare.28.6.1371","article-title":"Type 1 diabetes is associated with increased cyclooxygenase- and cytokine-mediated inflammation","volume":"28","author":"Basu","year":"2005","journal-title":"Diabetes Care"},{"key":"ref_17","first-page":"383","article-title":"Value of C-reactive protein and IL-6 measurements in type 1 diabetes mellitus","volume":"5","author":"Fawaz","year":"2009","journal-title":"Arch. Med. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1210\/jc.2007-2185","article-title":"Increased toll-like receptor (TLR) 2 and TLR4 expression in monocytes from patients with type 1 diabetes: Further evidence of a proinflammatory state","volume":"93","author":"Devaraj","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1002\/(SICI)1096-9136(199701)14:1<29::AID-DIA300>3.0.CO;2-V","article-title":"Impaired leucocyte functions in diabetic patients","volume":"14","author":"Delamaire","year":"1997","journal-title":"Diabet. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1159\/000233875","article-title":"Neutrophil and monocyte adherence in diabetes mellitus, alcoholic cirrhosis, uraemia and elderly patients","volume":"78","author":"Kelly","year":"1985","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/0168-8227(93)90112-I","article-title":"Evidence of ex vivo and in vitro impaired neutrophil oxidative burst and phagocytic capacity in type 1 diabetes mellitus","volume":"19","author":"Marhoffer","year":"1993","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1128\/IAI.00503-08","article-title":"Human polymorphonuclear neutrophil responses to Burkholderia pseudomallei in healthy and diabetic subjects","volume":"77","author":"Chanchamroen","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"479","DOI":"10.2337\/diacare.6.5.479","article-title":"Phagocytotic activity of monocytes from diabetic patients","volume":"6","author":"Katz","year":"1983","journal-title":"Diabetes Care"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1111\/j.1440-1681.2007.04729.x","article-title":"Role of macrophages in complications of type 2 diabetes","volume":"34","author":"Tesch","year":"2007","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1196\/annals.1447.053","article-title":"Evaluation of Cytokine Production from Peripheral Blood Mononuclear Cells of Type 1 Diabetic Patients: Importance of the Methodologic Approach","volume":"1150","author":"Foss","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.2337\/diacare.26.5.1535","article-title":"C-reactive protein and glycemic control in adults with diabetes","volume":"26","author":"King","year":"2003","journal-title":"Diabetes Care"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s00005-012-0210-1","article-title":"Inflammation, cytokines and insulin resistance: A clinical perspective","volume":"61","author":"Wieser","year":"2013","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.2337\/diab.43.11.1271","article-title":"Tumor necrosis factor alpha: A key component of the obesity-diabetes link","volume":"43","author":"Hotamisligil","year":"1994","journal-title":"Diabetes"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1177\/193229681200600303","article-title":"Upregulation of proinflammatory cytokine production in response to bacterial pathogen-associated molecular patterns in dogs with diabetes mellitus undergoing insulin therapy","volume":"6","author":"DeClue","year":"2012","journal-title":"J. Diabetes Sci. Technol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.vetimm.2012.06.027","article-title":"Evaluation of cytokines and hormones in dogs before and after treatment of diabetic ketoacidosis and in uncomplicated diabetes mellitus","volume":"148","author":"Drobatz","year":"2012","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_31","first-page":"1498","article-title":"Neutrophil adherence and movement in poorly and well-controlled diabetic dogs","volume":"45","author":"Latimer","year":"1984","journal-title":"Am. J. Vet. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5314","DOI":"10.1128\/IAI.66.11.5314-5321.1998","article-title":"1, 25-Dihydroxyvitamin D3 induces nitric oxide synthase and suppresses growth of Mycobacterium tuberculosis in a human macrophage-like cell line","volume":"66","author":"Rockett","year":"1998","journal-title":"Infect. Immun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7190","DOI":"10.4049\/jimmunol.178.11.7190","article-title":"IFN-\u03b3-and TNF-independent vitamin D-inducible human suppression of mycobacteria: The role of cathelicidin LL-37","volume":"178","author":"Martineau","year":"2007","journal-title":"J. Immunol."},{"key":"ref_34","first-page":"672","article-title":"Calcitriol modulates the effects of bone marrow-derived mesenchymal stem cells on macrophage functions","volume":"18","author":"Motlagh","year":"2015","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.3382\/ps\/pew186","article-title":"The immunomodulatory effect of vitamin D in chickens is dose-dependent and influenced by calcium and phosphorus levels","volume":"95","author":"Yitbarek","year":"2016","journal-title":"Poult. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5805","DOI":"10.3168\/jds.2016-12506","article-title":"Use of calcitriol to maintain postpartum blood calcium and improve immune function in dairy cows","volume":"100","author":"Lima","year":"2017","journal-title":"J. Dairy. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.cimid.2018.09.001","article-title":"Calcitriol increases nitric oxide production and modulates microbicidal capacity against Mycobacterium bovis in bovine macrophages","volume":"59","year":"2018","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.tvjl.2018.04.010","article-title":"Effect of calcitriol on in vitro whole blood cytokine production in critically ill dogs","volume":"236","author":"Jaffey","year":"2018","journal-title":"Vet. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.2460\/ajvr.79.10.1071","article-title":"Effects of calcitriol on apoptosis, toll-like receptor 4 expression, and cytokine production of endotoxin-primed canine leukocytes","volume":"79","author":"Jaffey","year":"2018","journal-title":"Am. J. Vet. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.2460\/ajvr.79.10.1064","article-title":"Effects of calcitriol on phagocytic function, toll-like receptor 4 expression, and cytokine production of canine leukocytes","volume":"79","author":"Jaffey","year":"2018","journal-title":"Am. J. Vet. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1579631","DOI":"10.1080\/2000625X.2019.1579631","article-title":"Serum vitamin D and diabetic foot complications","volume":"10","author":"Greenhagen","year":"2019","journal-title":"Diabet. Foot Ankle"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1515\/jpem-2016-0292","article-title":"Vitamin D status in Egyptian children with type 1 diabetes and the role of vitamin D replacement in glycemic control","volume":"30","author":"Hafez","year":"2017","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Savastio, S., Cadario, F., Genoni, G., Bellomo, G., Bagnati, M., Secco, G., Picchi, R., Giglione, E., and Bona, G. (2016). Vitamin D Deficiency and Glycemic Status in Children and Adolescents with Type 1 Diabetes Mellitus. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0162554"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1309\/AJCPJGZQX42BIAXL","article-title":"Low vitamin D levels correlate with the proinflammatory state in type 1 diabetic subjects with and without microvascular complications","volume":"135","author":"Devaraj","year":"2011","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s00592-008-0071-6","article-title":"High prevalence of vitamin D deficiency in type 1 diabetes mellitus and healthy children","volume":"46","author":"Bener","year":"2009","journal-title":"Acta Diabetol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Giri, D., Pintus, D., Burnside, G., Ghatak, A., Mehta, F., Paul, P., and Senniappan, S. (2017). Treating vitamin D deficiency in children with type I diabetes could improve their glycaemic control. BMC Res. Notes, 10.","DOI":"10.1186\/s13104-017-2794-3"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"em69","DOI":"10.29333\/ejgm\/93167","article-title":"Effect of vitamin D supplement therapy on HbA1C and IGF-1 levels in children with type 1 diabetes mellitus and vitamin D deficiency","volume":"15","author":"Dehkordi","year":"2018","journal-title":"Electron. J. Gen. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1111\/pedi.12595","article-title":"Improvements in peripheral vascular function with vitamin D treatment in deficient adolescents with type 1 diabetes","volume":"19","author":"Deda","year":"2018","journal-title":"Pediatr. Diabetes"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s12966-023-01460-y","article-title":"Modelling count, bounded and skewed continuous outcomes in physical activity research: Beyond linear regression models","volume":"20","author":"Akram","year":"2023","journal-title":"Int. J. Behav. Nutr. Phys. Act."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1046\/j.1365-2796.2002.00932.x","article-title":"Diabetes and advanced glycation endproducts","volume":"251","author":"Vlassara","year":"2002","journal-title":"J. Intern. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1196\/annals.1338.067","article-title":"Role of advanced glycation end products and their receptors in development of diabetic neuropathy","volume":"1043","author":"Wada","year":"2005","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.diabres.2004.09.004","article-title":"Advanced glycation endproducts\u2014Role in pathology of diabetic complications","volume":"67","author":"Ahmed","year":"2005","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Khalid, M., Petroianu, G., and Adem, A. (2022). Advanced glycation end products and diabetes mellitus: Mechanisms and perspectives. Biomolecules, 12.","DOI":"10.3390\/biom12040542"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.rvsc.2007.05.013","article-title":"Advanced glycation end products and sorbitol in blood from differently compensated diabetic dogs","volume":"84","author":"Comazzi","year":"2008","journal-title":"Res. Vet. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1939-1676.1993.tb03183.x","article-title":"Fructosamine. A new parameter for diagnosis and metabolic control in diabetic dogs and cats","volume":"7","author":"Reusch","year":"1993","journal-title":"J. Vet. Intern. Med."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Norris, O., and Schermerhorn, T. (2022). Relationship between HbA1c, fructosamine and clinical assessment of glycemic control in dogs. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0264275"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"233","DOI":"10.2460\/ajvr.81.3.233","article-title":"Comparison of serum fructosamine and glycated hemoglobin values for assessment of glycemic control in dogs with diabetes mellitus","volume":"81","author":"Magna","year":"2020","journal-title":"Am. J. Vet. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e244","DOI":"10.1002\/vetr.244","article-title":"Evaluation of fructosamine concentration as an index marker for glycaemic control in diabetic dogs","volume":"190","author":"Zeugswetter","year":"2022","journal-title":"Vet. Rec."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1093\/ndt\/gfi254","article-title":"Vitamin D decreases NF\u03baB activity by increasing I\u03baB\u03b1 levels","volume":"21","author":"Shany","year":"2006","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jsbmb.2006.07.008","article-title":"The Vitamin D analogue TX 527 blocks NF-\u03baB activation in peripheral blood mononuclear cells of patients with Crohn's disease","volume":"103","author":"Stio","year":"2007","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1210\/me.2003-0344","article-title":"Identification of a functional vitamin D response element in the human insulin-like growth factor binding protein-3 promoter","volume":"18","author":"Peng","year":"2004","journal-title":"Mol. Endocrinol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1530\/eje.0.1500591","article-title":"Inhibition of prostate cell growth by BXL-628, a calcitriol analogue selected for a phase II clinical trial in patients with benign prostate hyperplasia","volume":"150","author":"Crescioli","year":"2004","journal-title":"Eur. J. Endocrinol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1111\/j.1365-2362.2008.01977.x","article-title":"Calcitriol blunts pro-atherosclerotic parameters through NF\u03baB and p38 in vitro","volume":"38","author":"Talmor","year":"2008","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"86","DOI":"10.2478\/v10039-010-0012-9","article-title":"Vitamin D derivatives: Calcitriol and tacalcitol inhibits interleukin-6 and interleukin-8 expression in human nasal polyp fibroblast cultures","volume":"55","author":"Potyka","year":"2010","journal-title":"Adv. Med. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"F1059","DOI":"10.1152\/ajprenal.00051.2008","article-title":"Calcitriol blunts the deleterious impact of advanced glycation end products on endothelial cells","volume":"294","author":"Talmor","year":"2008","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.4049\/jimmunol.1102412","article-title":"Vitamin D inhibits monocyte\/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1","volume":"188","author":"Zhang","year":"2012","journal-title":"J. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"105477","DOI":"10.1016\/j.tvjl.2020.105477","article-title":"Immune function and serum vitamin D in shelter dogs: A case-control study","volume":"261","author":"Allison","year":"2020","journal-title":"Vet. J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40575-020-00090-y","article-title":"Effects of calcitriol on oxidative burst, phagocytic function, and leukocyte cytokine production in shelter dogs","volume":"7","author":"Jaffey","year":"2020","journal-title":"Canine Med. Genet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1177\/147323000303100604","article-title":"Comparative efficacy of oral and intravenous calcitriol treatment in haemodialysis patients: Effects on serum biochemistry and cytokine levels","volume":"31","author":"Borazan","year":"2003","journal-title":"J. Int. Med. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.cyto.2012.10.001","article-title":"Calcitriol downregulates TNF-alpha and IL-6 expression in cultured placental cells from preeclamptic women","volume":"61","author":"Diaz","year":"2013","journal-title":"Cytokine"},{"key":"ref_71","first-page":"5437","article-title":"Calcitriol plays a protective role in diabetic nephropathy through anti-inflammatory effects","volume":"7","author":"Mao","year":"2014","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.2337\/diabetes.51.8.2481","article-title":"Phagocytosis of apoptotic cells by macrophages from NOD mice is reduced","volume":"51","author":"Huang","year":"2002","journal-title":"Diabetes"},{"key":"ref_73","first-page":"227","article-title":"Decreased phagocytosis and antibody-dependent cellular cytotoxicity (ADCC) in type-1 diabetes","volume":"35","author":"Sabioncello","year":"1981","journal-title":"Biomedicine"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.3389\/fimmu.2019.02811","article-title":"Impaired Phagocytosis in Dendritic Cells From Pediatric Patients With Type 1 Diabetes Does Not Hamper Their Tolerogenic Potential","volume":"10","author":"Murillo","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.2337\/diabetes.55.04.06.db05-1434","article-title":"Survival benefits of intensive insulin therapy in critical illness: Impact of maintaining normoglycemia versus glycemia-independent actions of insulin","volume":"55","author":"Ellger","year":"2006","journal-title":"Diabetes"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5329","DOI":"10.1210\/en.2003-0697","article-title":"Metabolic, endocrine, and immune effects of stress hyperglycemia in a rabbit model of prolonged critical illness","volume":"144","author":"Weekers","year":"2003","journal-title":"Endocrinology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"244","DOI":"10.3181\/00379727-211-43967","article-title":"1, 25-dihydroxyvitamin D3 stimulates phagocytosis but suppresses HLA-DR and CD13 antigen expression in human mononuclear phagocytes","volume":"211","author":"Tokuda","year":"1996","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.intimp.2015.11.033","article-title":"Vitamin D3 enhances bactericidal activity of macrophage against Pseudomonas aeruginosa","volume":"30","author":"Nouari","year":"2016","journal-title":"Int. Immunopharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1111\/j.1365-3083.1993.tb03237.x","article-title":"1, 25-Dihydroxyvitamin D3 exerts opposing effects to IL-4 on MHC class-II antigen expression, accessory activity, and phagocytosis of human monocytes","volume":"38","author":"Xu","year":"1993","journal-title":"Scand. J. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1046\/j.1365-2567.1997.00148.x","article-title":"Effects of 1\u03b1, 25-dihydroxyvitamin D3 and cytokines on the expression of MHC antigens, complement receptors and other antigens on human blood monocytes and U937 cells: Role in cell differentiation, activation and phagocytosis","volume":"90","author":"Spittler","year":"1997","journal-title":"Immunology"}],"container-title":["Veterinary Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-7381\/11\/5\/193\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:35:05Z","timestamp":1760106905000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-7381\/11\/5\/193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,28]]},"references-count":80,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["vetsci11050193"],"URL":"https:\/\/doi.org\/10.3390\/vetsci11050193","relation":{},"ISSN":["2306-7381"],"issn-type":[{"value":"2306-7381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,28]]}}}