Enhanced and coordinated in vivo expression of inflammatory cytokines and nitric oxide synthase by chondrocytes from patients with osteoarthritis

Objective. To evaluate the sites of expression of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and inducible nitric oxide synthase (iNOS) in patients with inflammatory and degenerative joint diseas es. Methods. Cytokines and iNOS were detected by immunohistochemistry analysis of synovial and cartilage biopsy specimens obtained at knee arthroscopy in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), osteoar thritis (OA), and traumatic knee arthritis. Cytokine and iNOS expression wa s quantified using computerized image analysis. Results. IL-1 beta, TNF alpha, and iNOS were highly expressed by synovial c ells (lining layer cells, infiltrating leukocytes, endothelial cells) from patients with inflammatory arthritides and significantly less by synovial c ells from patients with OA and traumatic arthritis. In contrast, the latter patients showed high chondrocyte expression of cytokines and iNOS while RA and PsA patients had only minor chondrocyte positivity. In both joint comp artments, IL-1 beta expression, TNF alpha expression, and iNOS expression w ere strongly correlated. Conclusion, The enhanced and coordinated expression of IL-1 beta, TNF alpha , and iNOS by chondrocytes strongly supports the hypothesis that chondrocyt es are the major site of production of mediators of inflammation in human O A, thus playing a primary role in the pathogenesis of this disease.