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

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‐α and IL‐1β production were measured in plasma. Rolipram was the most potent inhibitor of cytokine production (IC₅₀ 0.84 and 4.68 μm for TNF‐α and IL‐1β, respectively) with almost complete inhibition of TNF‐α, but inhibited IL‐1β by only 39.46%. Azithromycin produced almost complete inhibition of both cytokines, but tended to be less potent than rolipram (IC₅₀ 10.66 and 17.4 μm for TNF‐α and IL‐1β, respectively). Metformin inhibited TNF‐α production with similar potency to rolipram and azithromycin (IC₅₀ 3.35 μm ) but showed significantly lower efficacy (45.93%; P < 0.05), and had no inhibitory effect on IL‐1β. Ethyl pyruvate was the least potent (IC₅₀ 68.35 μm and >10 mm for TNF‐α and IL‐1β 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.