Effect of cytokines and anti-arthritic drugs on glycosaminoglycan synthesis by bovine articular chondrocytes

Abstract

The effect of cytokines (interleukin-1 alpha, interleukin-1 beta, and tumor necrosis factor alpha) and several anti-arthritic drugs on glycosaminoglycan synthesis and secretion into medium by bovine articular chondrocytes was examined. Sulfated glycosaminoglycans (S-GAG) were measured by a modified 1,9-dimethylmethylene blue (DMB) dye binding assay. Hyaluronate (HA) was measured by an inhibition ELISA based on specific binding to a proteoglycan. All three cytokines caused a dose-dependent decrease in S-GAG production and a dose-dependent increase in HA production. Non-steroidal anti-inflammatory drugs (NSAIDs, indomethacin, naproxen, and piroxicam, 1 microM) could not reverse the effect of IL-1 alpha on inhibiting S-GAG and stimulating HA synthesis. The anti-inflammatory steroid (dexamethasone, 1 microM) depressed HA synthesis by 50-70% in the absence or presence of IL-1 alpha. Dexamethasone depressed S-GAG synthesis by 20-30% in the absence or presence of IL-1 alpha. Therefore, none of the tested anti-rheumatic drugs reversed the cytokine mediated changes in glycosaminoglycan synthesis by bovine chondrocytes.