Three human cytokines (interleukin-1 alpha, interleukin-1 beta and tumor necrosis factor-alpha), added into the medium of bovine or rabbit articular cartilage explant cultures, stimulated the synthesis and activation of various proteinases. Proteoglycan degradation, measured by assaying for sulfated glycosaminoglycans released into the medium, was correlated with the proteinase stimulation. Several antirheumatic drugs were tested in a similar tissue culture system as potential inhibitors of the interleukin-1 alpha mediated stimulation of proteinase and PGE2 syntheses. Arteparon, Dexamethasone, Ibuprofen, Indomethacin, Levamisole, Naproxen, Phenylbutazone, Prednisolone, Piroxicam, Rumalon, Tamoxifen and Diclofenac were essentially ineffective in inhibiting the interleukin-1 alpha mediated induction of proteinase synthesis and sulfated glycosaminoglycan release, although some of them inhibited PGE2 synthesis. Two antimalarial drugs showed some inhibition, but only at higher concentrations.
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