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

Abstract

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‐1β ‐stimulation with higher NO production than RA cartilage, whereas there was no difference in NO synthesis between OA and RA samples when stimulated by TNFα or LPS. Interleukin‐1 receptor antagonist (IL‐1Ra) production was higher in RA cartilage than in OA cartilage, and its production was increased by NO synthase inhibitor 1400W.

Conclusion: IL‐1β 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.

• nitric oxide
• osteoarthritis
• rheumatoid arthritis
• interleukin‐1