Lack of causal relationship between inducibility/severity of adjuvant arthritis in the rat and disease associated changes in production of nitric oxide by macrophages.

Z Zídek, D Franková, B Otová

Institute of Pharmacology, Academy of Sciences of Czech Republic, Prague.

OBJECTIVE--To investigate the formation of nitric oxide (NO) by peritoneal macrophages in three inbred strains of rats differing both in their susceptibility to the induction of adjuvant arthritis (AA) and in the severity of the disease. METHODS--AA was induced by intraplantar injection of Mycobacterium tuberculosis (M.tb) in paraffin oil. Isolated peritoneal macrophages were cultured for 24 hours and supernatants were assayed for nitrite using Griess reagent. RESULTS--All rats of the LEW and BN strains became diseased, but the F344 strain included both responders and non-responders. 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 animals, regardless of the absence or presence of AA, and did not parallel its severity. Altered production of NO by macrophages from adjuvant treated rats was normalised in vitro in the presence of lipopolysaccharide. CONCLUSIONS--Our findings suggest that the activity of constitutive or inducible NO synthase in peritoneal macrophages cannot be regarded as a determinant of genetically controlled disease inducibility and severity. Secretion of latent forms of certain NO downregulatory factors during development of AA may be implicated.

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