LACK OF CAUSAL RELATIONSHIP BETWEEN INDUCIBILITY SEVERITY OF ADJUVANTARTHRITIS IN THE RAT AND DISEASE-ASSOCIATED CHANGES IN PRODUCTION OF NITRIC-OXIDE BY MACROPHAGES

Objective-To investigate the formation of nitric oxide (NO) by periton eal macrophages in three inbred strains of rats differing both in thei r susceptibility to the induction of adjuvant arthritis (AA) and in th e severity of the disease. Methods-AA was induced by intraplantar inje ction of Mycobacterium tuberculosis (M.tb) in paraffin oil. Isolated p eritoneal macrophages were cultured for 24 hours and supernatants were assayed for nitrite using Griess reagent. Results-Ah rats of the LEW and BN strains became diseased, but the F344 strain included both resp onders and nonresponders. No significant interstrain differences were observed in the generation of NO by macrophages from control animals. Nitrite concentrations were remarkably enhanced in all M.tb treated an imals, regardless of the absence or presence of AA, and did not parall el its severity. Altered production of NO by macrophages from adjuvant treated rats was normalised in vitro in the presence of lipopolysacch aride. Conclusions-Our findings suggest that the activity of constitut ive or inducible NO synthase in peritoneal macrophages cannot be regar ded as a determinant of genetically controlled disease inducibility an d severity. Secretion of latent forms of certain NO downregulatory fac tors during development of AA may be implicated.