The effect of recombinant tumor necrosis factor-alpha on superoxide and metalloproteinase production by synovial cells and chondrocytes.

We studied the effect of recombinant tumor necrosis factor-alpha (rTNF-alpha) on the production of superoxide and metalloproteinase by rheumatoid synovial cells or osteoarthritis chondrocytes. rTNF-alpha significantly inhibited superoxide generation by osteoarthritis chondrocytes and rheumatoid synovial cells at a concentration of 23 U/ml. On the other hand, rTNF-alpha at a concentration of 1500 U/ml significantly enhanced superoxide production by rheumatoid synovial cells, osteoarthritis synovial cells and osteoarthritis chondrocytes, respectively. Metalloproteinase released by rheumatoid synovial cells and chondrocytes derived from osteoarthritis patients were stimulated by rTNF-alpha at a concentration of 94 U/ml. rTNF-alpha at the highest concentration (15000 U/ml) significantly inhibited metalloproteinase release by rheumatoid synovial cells. The enhancing effect of rTNF-alpha at higher concentrations on superoxide production by rheumatoid synovial cells and osteoarthritis chondrocytes was time dependent. These results suggest that rTNF-alpha has a biphasic effect on superoxide and metalloproteinase production, and hence may play an important role in the pathogenesis of inflammatory joint diseases.