SUPPRESSION OF ADJUVANT-INDUCED ARTHRITIS BY SELECTIVE-INHIBITION OF INDUCIBLE NITRIC-OXIDE SYNTHASE

Adjuvant-induced arthritis is a model of chronic inflammation that exh ibits several pathological changes similar to those occurring in rheum atoid arthritis, an autoimmune disease in humans characterized by chro nic inflammation of the joints. We have examined the role of inducible nitric oxide synthase in producing the pathological changes associate d with adjuvant-induced arthritis. Plasma nitrite concentrations were maximally elevated 14 days following adjuvant administration compared to untreated control animals. Arthritic changes in the paw were first observed between days 10-12 and were maximally elevated 21 days follow ing adjuvant administration. inducible nitric oxide synthase immunorea ctivity was found localized in the synovial tissue from adjuvant-treat ed rats, while untreated controls exhibited no inducible nitric oxide synthase staining. Two selective inducible nitric oxide synthase inhib itors, aminoguanidine and N-iminoethyl-L-lysine, suppressed the increa se in plasma nitrite levels and joint inflammation associated with adj uvant-induced arthritis in a dose-dependent manner. N-Iminoethyl-L-lys ine attenuated the inducible nitric oxide synthase immunoreactivity in adjuvant-treated rats. Blood pressure was not affected by the highest dose of N-iminoethyl-L-lysine administered in the drinking water, ind icating a lack of inhibition of constitutive nitric oxide synthase.