Effects of anti-inflammatory drugs on catabolin-induced cartilage destruction in vitro.

Catabolin/Interleukin 1 (CAT-IL-1) comprises a family of acidic proteins produced by stimulated monocytes and inflamed synovium which cause the release of proteoglycans and collagen from living cartilage in vitro. The possible relevance of these proteins as mediators of joint destruction in animal models of joint damage and in arthritic disease in man has yet to be determined. To establish if conventional or novel anti-inflammatory (AI) agents could modify the actions of CAT-IL-1 and thus be useful for understanding the mode of action of these components, the effects were determined of a range of AI compounds on the release by CAT-IL-1 of proteoglycans (PG's) from bovine nasal cartilage. In vitro, conventional non-steroidal anti-inflammatory (NSAI) compounds were, with the exception of 10-100 microM hydroxychloroquine, weak (e.g. diclofenac, indomethacin, fenclofenac, effective at concentrations of 100-500 microM), or with some drugs actually ineffective, as inhibitors of CAT-IL-1-mediated PG release. Antioxidants were ineffective as inhibitors of this PG release. Drugs which modify gene transcription were potent inhibitors of CAT-IL-1-induced PG release, emphasizing the importance of gene expression in the actions of these mediators. The importance of prostaglandin metabolism on CAT-IL-1 actions and the in vivo effects of AI are discussed.