The synovial activation of chondrocytes: evidence for complex cytokine interactions involving a possible novel factor.

Preparations of lapine synovial 'chondrocyte activating factors' (CAF) were analyzed for the presence of individual cytokines which modulate the production of neutral metalloproteinases (NMPs) and prostaglandin E2 (PGE2) by articular chondrocytes. A combination of different biochemical analyses suggested that synovial fibroblasts secrete IL-1 alpha, which activated chondrocytes directly, bFGF, which potentiated the activity of IL-1, and TGF-beta 1, which produced a bivalent response. TGF-beta 1 suppressed NMP synthesis by chondrocytes, but enhanced PGE2 synthesis. The IL-1 receptor antagonist protein (IRAP) eliminated chondrocyte activation by IL-1, but only partially inhibited activation by CAF. Thus, CAF may contain a cytokine in addition to IL-1 which activates chondrocytes. This putative additional factor was more thermosensitive than IL-1, and had an apparent molecular weight of approx. 20,000 when estimated by size exclusion chromatography. Of a variety of purified cytokines tested for their ability to induce NMPs in chondrocytes, only IL-1 was active. This favours the possibility that the activity which resists suppression by IRAP reflects the presence of a novel cytokine.