title: Neutrophil and cytokine dysregulation in hyperinsulinemic obese horses.
abstract: Equine metabolic syndrome is characterized by obesity and regional adiposity coupled with evidence of recurrent laminitis. Although inflammation has been well characterized in several experimental models of acute laminitis, the inflammatory events associated with endocrinopathic laminitis are not well documented. The aim of this study was to characterize selected markers of inflammation in horses with clinical evidence of equine metabolic syndrome (EMS). Neutrophil phagocytosis and oxidative burst, as well as endogenous and stimulated cytokine expression were evaluated. A marked increase in neutrophil reactive oxygen species production upon phagocytosis was observed in horses with EMS that was strongly correlated to the blood insulin concentration. Increased oxidative burst activity of neutrophils in hyperinsulinemic horses may predispose horses with metabolic syndrome to laminitis. In contrast, peripheral blood cells of obese hyperinsulinemic horses showed decreased endogenous proinflammatory cytokine gene expression (IL-1 and IL-6) and similar cytokine response following immune stimulation compared to that of control horses. This may suggest that, unlike in people, cytokine-mediated inflammation does not increase in direct response to obesity or insulin resistance in horses. This species-specific disparity may explain the difference in clinical outcomes observed in obese horses compared to obese people.
authors.affiliation: Department of Veterinary Clinical Sciences, 002 BVMTH, Oklahoma State University, Stillwater, OK 74078, USA.
authors.forename: Todd C
authors.initials: TC
authors.lastname: Holbrook
authors.forename: Ty
authors.initials: T
authors.lastname: Tipton
authors.forename: Dianne
authors.initials: D
authors.lastname: McFarlane
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000032:analysis; D016207:Cytokines / Q000502:physiology*; D005260:Female; D006734:Horse Diseases / Q000276:immunology* / Q000503:physiopathology; D006736:Horses / Q000276:immunology; D006946:Hyperinsulinism / Q000276:immunology / Q000503:physiopathology / Q000662:veterinary*; D007375:Interleukin-1 / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D008297:Male; D009504:Neutrophils / Q000737:chemistry / Q000502:physiology*; D009765:Obesity / Q000276:immunology / Q000503:physiopathology / Q000662:veterinary*; D010587:Phagocytosis / Q000502:physiology; D017382:Reactive Oxygen Species / Q000032:analysis; D016897:Respiratory Burst / Q000502:physiology; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000521:alpha-MSH / Q000097:blood
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; D000521:alpha-MSH; D002097:C-Reactive Protein