2016 ACVIM Forum Research Abstract Program

Mixed models were fit for percent change from baseline values for each outcome using PROC MIXED (SAS, SAS Institute. Cary, NC). Significant decreases in DPpl max , R L and significant increases in C dyn were identified at all dosages and were accompanied by increased P a O 2 and decreased P a CO 2 , substantiating improved ventilation. We conclude that intravenous infusion of MgSO 4 has immediate bronchodilatory effects in horses making this therapy a valuable adjunct in horses with signs of respiratory distress referable to bronchoconstriction. E-type prostaglandins (PGEs) play diverse roles throughout the body, including regulation of gastrointestinal (GI) homeostasis and modulation of inflammation. To treat inflammation, anti-inflammatory medications including nonsteroidal anti-inflammatory drugs (NSAIDs) are designed to inhibit prostaglandin production. Unfortunately, potential adverse effects of NSAID use in horses include gastric ulceration and right dorsal colitis. To prevent and treat NSAID-associated GI injury, equine practitioners commonly administer the PGE 1 analog, misoprostol. In addition to serving as a gastroprotectant, misoprostol has been shown to have antiinflammatory effects in cell models, potentially by increasing intracellular cyclic AMP (cAMP). Elevated cAMP is known to dampen leukocyte effector functions that can damage host tissues, including cellular adhesion, tissue infiltration, and cytokine and superoxide production. The effects of misoprostol on equine leukocyte effector functions are undetermined. Thus, the purpose of this study was to determine the effects of misoprostol on equine leukocyte proinflammatory cytokine and superoxide production in vitro. Equine leukocytes were isolated from whole blood and stimulated with lipopolysaccharide (LPS) in the presence or absence of misoprostol. Misoprostol at concentrations of 1-10 lM significantly inhibited tumor necrosis factor-a, interleukin-1b, and interleukin-6 mRNA production, as measured by qPCR. Misoprostol also elicited concentration-dependent decreases in neutrophil superoxide production in response to granulocyte-monocyte colony-stimulating factor priming and LPS stimulation, as measured by luminol-enhanced chemiluminescence. From this data we conclude that misoprostol produces anti-inflammatory effects in equine leukocytes in vitro, paving the way for in vivo studies investigating misoprostol as an anti-inflammatory treatment in horses.