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Osteoarthritis Cartilage. 2002 Apr;10(4):327-32.

Effects of TNFalpha-antagonists on nitric oxide production in human cartilage.

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The Immunopharmacological Research Group, Medical School, University of Tampere, Tampere, Finland.



Nitric oxide (NO) produced by cartilage and synovial membrane is implicated in the pathogenesis of osteoarthritis (OA) and rheumatoid arthritis (RA). In inflamed joints NO is synthesized in response to proinflammatory cytokines and it is involved in the joint destruction. The aim of the present study was to investigate the effects of TNFalpha-antagonists infliximab and etanercept on NO production in human cartilage.


Cartilage specimen obtained from OA patients undergoing knee replacement surgery were studied for iNOS expression and NO production in organ culture to allow intact chondrocyte-matrix interactions. TNFalpha and soluble TNFalpha receptor release was measured by ELISA.


Osteoarthritic cartilage produced NO spontaneously and its production was enhanced by proinflammatory cytokines TNFalpha (tumor necrosis factor alpha), IL-1beta (interleukin-1beta), IL-17 (interleukin-17) and by bacterial lipopolysaccharide (LPS). TNFalpha-antagonists infliximab and etanercept inhibited TNFalpha-induced NO production in a dose dependent manner but they had no effect on IL-1beta-, IL-17- and LPS-stimulated NO synthesis. TNFalpha and soluble TNFalpha receptors (sTNFRI and sTNFRII) were produced by human osteoarthritic cartilage. A neutralizing antibody against soluble TNFRI enhanced spontaneous NO production whereas an antibody against soluble TNFRII had no effect.


TNFalpha-antagonists infliximab and etanercept suppressed TNFalpha-induced NO production. This effect was not seen on IL-1-, IL-17- or LPS-induced NO production suggesting that TNFalpha is not an autacoid mediator in these processes. The studies with neutralizing antibodies against soluble TNFRI suggest that endogenous cartilage-derived TNFalpha-antagonists modulate NO production in osteoarthritic cartilage.

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