Nonsteroidal antiinflammatory drugs: Effects on normal and interleukin 1 treated human articular chondrocyte metabolism in vitro

Objective. To test the effects of nonsteroidal antiinflammatory drugs (NSAID), naproxen, ibuprofen and diclofenac, and salicylates on normal and interleukin 1 (IL-1) treated human articular chondrocyte metabolism in vitro. Methods. Normal adult human articular chondrocytes were isolated and cultured as primary monolayers; the cells were treated with NSAID and salicylates at low and high plating density for assessing effects on proliferation and matrix synthesis and IL-1 modulated cell metabolism, respectively. Results. Cell proliferation was inhibited by ibuprofen and high doses of salicylates. Glycosaminoglycan (GAG) synthesis was stimulated by ibuprofen at 10 μg/ml but was not changed by any other drugs at similarly low concentrations; at medium to high concentrations, only the salicylates inhibited GAG synthesis. Collagen synthesis was unaffected by any drug at the concentrations tested. IL-1 induced prostaglandin E₂ release was completely inhibited by the NSAID and partially inhibited by the salicylates. IL-1 induced IL-6 release was inhibited by ibuprofen and the salicylates whereas IL-1 induced APMA-activated collagenase was only inhibited by the salicylates. Conclusion. Normal human chondrocytes respond differentially to naproxen, ibuprofen, diclofenac, and the salicylates; these observations suggest that each drug may exhibit unique attributes with respect to longterm efficacy on cartilage metabolism.