Synovial fluid levels of tumor necrosis factor alpha and oncostatin M correlate with levels of markers of the degradation of crosslinked collagen andcartilage aggrecan in rheumatoid arthritis but not in osteoarthritis

Objective. To compare synovial fluid (SF) levels of oncostatin M (OSM), tum or necrosis factor alpha (TNF alpha), and interleukin-6 (IL-6) in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to determine whi ch correlate best with SF levels of antigenic keratan sulfate (Ag KS), a ma rker of aggrecan catabolism, and pyridinium crosslinks, markers of the degr adation of mature collagen molecules. Methods. SF was drawn from the knee joints of patients with RA (n = 31) or OA (n = 31.), Levels of Ag KS, D-pyridinoline (D-Pyr), pyridinoline (Pyr), OSM, TNF alpha, and IL-6 were measured by enzyme-linked immunosorbent assay . Results. RA patients had higher median SF levels of OSM, TNF alpha, IL-6, a nd Pyr, but a lower median level of D-Pyr, than OA patients. In both groups , IL-6 levels correlated positively with those of OSM and TNF alpha, Howeve r, the correlation between levels of OSM and TNF alpha was only significant in the RA group. Ag KS and Pyr levels correlated positively in RA but not in OA. The correlation between TNF alpha and Ag KS was positive in RA and n egative in OA. Further, in RA, OSM and IL-6 levels correlated strongly with Pyr and Ag KS levels but not with D-Pyr levels, while there were no strong correlations in OA for OSM or IL-6 levels with Pyr, Ag Ks, or D-Pyr levels . Conclusion. This in vivo study suggests that TNF alpha and other proinflamm atory cytokines are involved in the up-regulation of the coordinated degrad ation of cartilage aggrecan and collagen in RA, Further, OSM may act synerg istically,vith other proinflammatory cytokines in up-regulating the product ion of metalloproteinases by chondrocytes in rheumatoid joints.