SYNOVIAL ACTIVATION OF CHONDROCYTES - EVIDENCE FOR COMPLEX CYTOKINE INTERACTIONS

Synoviocytes secrete factors which induce the synthesis of neutral metalloproteinases (NMP) and prostaglandin E2 (PGE2) by chondrocytes in a response called "chondrocyte activation". We analyzed synovial chondrocyte activating factors (CAF) for the presence of cytokines which modulated the NMP production by articular chondrocytes. These studies suggested the presence of several other cytokines in addition to interleukin-1 (IL-1). Both resting and activated synoviocytes contained mRNA for basic fibroblast growth factor (bFGF) which is a synergist for IL-1 induced NMP production, and secreted bFGF into their culture media. They also expressed mRNA for transforming growth factor beta (TGF-beta) which inhibits IL-1 induced NMP production. These cells also produce tumor necrosis factor alpha (TNF-alpha) and trace amounts of interleukin-6 (IL-6). In addition to these there is evidence for a synovial activator of chondrocytes which is distinct from IL-1. Since a number of recombinant cytokines including TNF-alpha, IL-6 and bFGF failed to activate chondrocytes, this could be a novel cytokine.