Regulation of nitric oxide production in osteoarthritic and rheumatoid cartilage -: Role of endogenous IL-1 inhibitors

Objective: To investigate the endogenous regulation of interleukin-1 (IL-1) cytokine network in osteoarthritic (OA) and rheumatoid (RA) cartilage in relation to nitric oxide (NO) production. Methods: Cartilage specimen obtained from OA and RA patients undergoing knee replacement surgery were studied for iNOS expression, NO and IL-1 antagonist production in tissue culture. Results: OA cartilage responded to IL-1beta-stimulation with higher NO production than RA cartilage, whereas there was no difference in NO synthesis between OA and RA samples when stimulated by TNFalpha or LPS. Interleukin-1 receptor antagonist (IL-1Ralpha) production was higher in RA cartilage than in OA cartilage, and its production was increased by NO synthase inhibitor 1400W. Conclusion: IL-1beta is a potent stimulator of NO production by the iNOS pathway in RA and more pronouncedly in OA cartilage. This process is regulated by cartilage derived IL-1 antagonists, and is implicated in cartilage destruction and synovial inflammation in OA and RA joints.