Anti-inflammatory effects of four potential anti-endotoxaemic drugs assessed in vitro using equine whole blood assays

作者：Bauquier J R; Tudor E; Bailey S R^*

来源：Journal of Veterinary Pharmacology and Therapeutics, 2015, 38(3): 290-296.

DOI：10.1111/jvp.12182

Despite the severity and common occurrence of equine endotoxaemia, the available anti-endotoxic treatments do not effectively target key inflammatory mechanisms such as leucocyte activation and cytokine production. In this study, four compounds with potential anti-endotoxic effects, namely rolipram, azithromycin, ethyl pyruvate and metformin, were investigated in vitro using equine whole blood stimulated with bacterial lipopolysaccharide. TNF- and IL-1 production were measured in plasma. Rolipram was the most potent inhibitor of cytokine production (IC50 0.84 and 4.68m for TNF- and IL-1, respectively) with almost complete inhibition of TNF-, but inhibited IL-1 by only 39.46%. Azithromycin produced almost complete inhibition of both cytokines, but tended to be less potent than rolipram (IC50 10.66 and 17.4m for TNF- and IL-1, respectively). Metformin inhibited TNF- production with similar potency to rolipram and azithromycin (IC50 3.35m) but showed significantly lower efficacy (45.93%; P<0.05), and had no inhibitory effect on IL-1. Ethyl pyruvate was the least potent (IC50 68.35m and >10mm for TNF- and IL-1 production, respectively). Further work is required to investigate whether these or related compounds may have potential use in the treatment of equine endotoxaemia in vivo.

• 出版日期2015-6