title: Upregulation of proinflammatory cytokine production in response to bacterial pathogen-associated molecular patterns in dogs with diabetes mellitus undergoing insulin therapy.
abstract: BACKGROUND
  Metabolic alterations associated with diabetes mellitus alter innate immunity. Dogs often develop infectious or inflammatory complications related to diabetes mellitus, yet little is known about the effects of diabetes mellitus on the immune system in this species.
  
  
  METHODS
  Prospective evaluation in dogs with poorly regulated spontaneous type 1 diabetes mellitus (T1DM). In vitro leukocyte cytokine response to lipopolysaccharide (LPS), lipoteichoic acid (LTA), and peptidoglycan (PG) was compared between dogs with T1DM and healthy dogs. Additionally, the effect of acute in vitro glucose exposure on leukocyte tumor necrosis factor (TNF) production from healthy dogs was measured.
  
  
  RESULTS
  Leukocytes from dogs with T1DM had significantly greater TNF production after LTA and PG stimulation compared with leukocytes from healthy dogs. Leukocyte interleukin (IL)-6 production was greater after stimulation with LPS, LTA, PG, and phosphate-buffered saline in the T1DM group. No such difference was noted when evaluating IL-10 production between groups regardless of stimulant. Dogs with T1DM had significantly greater IL-6 to IL-10 production ratios than healthy dogs. Acute exposure to dextrose did not augment cytokine production from healthy canine leukocytes.
  
  
  CONCLUSIONS
  Dogs with T1DM have altered innate immunity characterized by upregulation of proinflammatory cytokine production without a concurrent change in anti-inflammatory cytokine production. This may be one explanation for the common infectious and inflammatory complications associated with T1DM in dogs.
authors: Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, Missouri 65211, USA. decluea@missouri.edu
authors: Amy E
authors: AE
authors: DeClue
authors: Jordan
authors: J
authors: Nickell
authors: Chee-hoon
authors: CH
authors: Chang
authors: Allison
authors: A
authors: Honaker
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000097:blood / Q000209:etiology / Q000276:immunology / Q000662:veterinary*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000662:veterinary*; D004283:Dog Diseases / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D004285:Dogs; D005260:Female; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007113:Immunity, Innate; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000276:immunology / Q000662:veterinary*; D018836:Inflammation Mediators / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D010457:Peptidoglycan / Q000494:pharmacology; D013682:Teichoic Acids / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D007004:Hypoglycemic Agents; D018836:Inflammation Mediators; D007328:Insulin; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C009900:lipoteichoic acid