NITRIC-OXIDE PRODUCTION DURING ADJUVANT-INDUCED AND COLLAGEN-INDUCED ARTHRITIS

Objective. To investigate the role of nitric oxide (NO) production and NO synthase (NOS) induction during adjuvant-induced arthritis (AIA) a nd collagen-induced arthritis (CIA) in Dark Agouti rats. Methods. Urin ary nitrate excretion and immune NOS (iNOS) messenger RNA (mRNA) expre ssion were measured in the joint, lymph node, spleen, and liver tissue s following the induction of either AIA or CIA. Results. Urinary nitra te excretion and iNOS mRNA expression increased substantially during j oint inflammation in both models of arthritis. However, the increases in urinary nitrate excretion and iNOS mRNA expression observed in the joint, liver, and spleen tissues during AIA were greater than those ob served during CIA, although iNOS induction in the lymph nodes was simi lar for both models. A prior injection with Mycobacterium bovis heat-s hock protein resulted in suppression of arthritis and NO production in AIA, but not in CIA. Conclusion. Differences in NO production during AIA versus CIA are a reflection of the fundamental pathophysiologic di fferences between these 2 models of arthritis. Thus, NO production in these 2 models could not be merely a nonspecific reaction to the adjuv ant injection, nor simply a byproduct of local inflammation in the joi nt.