title: Anti-inflammatory effects of four potential anti-endotoxaemic drugs assessed in vitro using equine whole blood assays.
abstract: 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.
authors.affiliation: Faculty of Veterinary Science, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: J R
authors.initials: JR
authors.lastname: Bauquier
authors.forename: E
authors.initials: E
authors.lastname: Tudor
authors.forename: S R
authors.initials: SR
authors.lastname: Bailey
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D017963:Azithromycin / Q000627:therapeutic use*; D019446:Endotoxemia / Q000188:drug therapy*; D006734:Horse Diseases / Q000188:drug therapy*; D006736:Horses; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides / Q000494:pharmacology; D008687:Metformin / Q000627:therapeutic use*; D011773:Pyruvates / Q000627:therapeutic use*; D020889:Rolipram / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D011773:Pyruvates; D014409:Tumor Necrosis Factor-alpha; C046522:ethyl pyruvate; D017963:Azithromycin; D008687:Metformin; D020889:Rolipram