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.
Rainsford
K D
KD
Anti-inflammatory Research Unit, Strangeways Research Laboratory, Cambridge, UK.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D006046:Gold / Q000494:pharmacology*; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism; D010720:Phosphines / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D013931:Thromboxanes / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D010720:Phosphines; D011453:Prostaglandins; D011509:Proteoglycans; D013931:Thromboxanes; D006046:Gold; D007930:Leucine