Effects of Anti-inflammatory Drugs on Interleukin 1-induced Cartilage Proteoglycan Resorption In-vitro: Inhibition by Aurothiophosphines but no Influence from Perturbed Eicosanoid Metabolism

A range of anti-inflammatory drugs having varying effects on eicosanoid metabolism and other actions was studied for their potential to inhibit alpha-interleukin 1 (IL-1)-induced cartilage proteoglycan resorption in-vitro. No significant effects on resorption were observed with inhibitors of cyclo-oxygenase, lipoxygenase or mixed inhibitors of both these enzymes, and no influence on IL-1 effects was observed with added eicosanoids. Among the clinically used disease modifying anti-arthritic agents, only auranofin and the immunoregulatory agent, tilomisole, were found effective in inhibiting resorption. Some auranofin analogues having chloride or nitrate leaving groups that inhibit DNA polymerase-alpha were found to be potent inhibitors of IL-1 induced resorption.