Evaluation of cytokines and hormones in dogs before and after treatment of diabetic ketoacidosis and in uncomplicated diabetes mellitus

Vet Immunol Immunopathol. 2012 Aug 15;148(3-4):276-83. doi: 10.1016/j.vetimm.2012.06.027. Epub 2012 Jul 7.


In human beings, diabetes mellitus (DM) and diabetic ketoacidosis (DKA) are recognized as proinflammatory states and dysregulation of cytokines has been linked to some potentially fatal complications. Cytokine profiles of dogs with DM or DKA have not been reported. The objectives of this study were to compare cytokine and hormone concentrations in dogs with DKA before and after resolution of ketoacidosis, to compare these concentrations before treatment of DKA to those measured in dogs with uncomplicated DM and healthy dogs, and to compare concentrations in dogs with uncomplicated DM to those measured in healthy dogs. 27 dogs were included in this prospective clinical study. 18 dogs had naturally-occurring disease (9 DKA and 9 DM) and 9 dogs were healthy. Serum GMCSF, IL-2, IL-4, IL-6, IL-7, CXCL8, IL-10, IL-15, IL-18, IFNγ, IP-10, TNFα, Monocyte Chemoattractant Protein-1 (MCP-1), Keratinocyte Chemoattractant (KC), glucagon, leptin, adiponectin, and resistin were assayed using Milliplex MAP Canine kits.(2)(,)(3) IL-18, resistin, and GMCSF concentrations were significantly higher in dogs with DKA before treatment compared to after resolution of ketoacidosis. CXCL8, MCP-1, KC, and resistin were significantly higher in DKA dogs compared to healthy controls, and KC was also significantly higher in DKA compared to DM dogs. Additionally, CXCL8 and MCP-1 were significantly higher in dogs with DM compared to healthy controls. Significant differences were not detected in concentrations of the other measured analytes, including glucagon. It is concluded that IL-18, resistin, GMCSF, and KC may be involved in the pathogenesis of canine DKA, and their importance in this pathogenesis may be as great as that of glucagon. Dysregulation of CXCL8 and MCP-1 may be involved in the pathogenesis of DM in dogs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokine CCL2 / blood
  • Chemokine CCL2 / immunology
  • Cytokines / blood*
  • Cytokines / immunology
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / immunology
  • Diabetes Mellitus / physiopathology
  • Diabetes Mellitus / veterinary*
  • Diabetic Ketoacidosis / blood
  • Diabetic Ketoacidosis / immunology
  • Diabetic Ketoacidosis / physiopathology
  • Diabetic Ketoacidosis / veterinary*
  • Dog Diseases / blood
  • Dog Diseases / immunology
  • Dog Diseases / physiopathology*
  • Dogs / blood
  • Dogs / immunology
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / blood
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Insulin / therapeutic use
  • Interleukin-18 / immunology
  • Interleukin-18 / physiology
  • Interleukin-8 / blood
  • Interleukin-8 / immunology
  • Male


  • Chemokine CCL2
  • Cytokines
  • Insulin
  • Interleukin-18
  • Interleukin-8
  • Granulocyte-Macrophage Colony-Stimulating Factor