Effects of anti-inflammatory drugs and agents that modify intracellular transduction signals or metabolic activities in inflammatory cells on interleukin-1 induced cartilage proteoglycan resorption in vitro.

The actions of (a) anti-inflammatory drugs possessing a wide range of chemical structures and pharmacological actions, and (b) agents which modify intracellular transduction signals or metabolic functions were investigated for their potential to modify in vitro the proteoglycan (PrGn) resorption in bovine nasal cartilage induced by interleukin-1 alpha (IL-1). It was found that: (a) none of the conventional anti-inflammatory agents exhibited any inhibitory effects on IL-1 induced resorption of PrGns with the exception of the weak effects observed with the iron chelator, desferrioxamine, a cryogenine derivative JB-1-0, and myalex; (b) the antitumour agent cisplatin was a potent inhibitor but the analogue, transplatin, which does not inhibit DNA synthesis was without effect; (c) suramin, an inhibitor of cartilage degrading enzymes from leucocytes, also inhibited IL-1 induced resorption, as did natural somatomedin C (insulin-like growth factor = IGF alpha) but not agents previously shown to inhibit the lymphocyte mitogenic responses to IL-1 (e.g. alpha-melanocyte stimulating hormone, phenylglyoxal); (d) while no effects were observed with drugs that alter the intracellular production of cyclic AMP, those which affect uptake of calcium ions did inhibit proteoglycan resorption by IL-1. The results suggest that IL-1 induced cartilage PrGn degradation can be regulated at the level of transcriptional production of intracellular PrGn degrading enzymes or their activity, regulating calcium uptake into chondrocytes or by overcoming the PrGn degradation from IL-1 by stimulating the synthesis of these macromolecules.