ALTERED IMMUNE-RESPONSES IN MICE LACKING INDUCIBLE NITRIC-OXIDE SYNTHASE

NITRIC oxide (NO) is important in many biological functions(1-5). It i s generated from L-arginine by the enzyme NO synthase (NOS), The cytok ine-inducible NOS (iNOS) is activated by several immunological stimuli , leading to the production of large quantities of NO which can be cyt otoxic(6). To define the biological role of iNOS further, we generated iNOS mutant mice. These are viable, fertile and without evident histo pathological abnormalities, However, in contrast to wild-type and hete rozygous mice, which are highly resistant to the protozoa parasite Lei shmania major infection, mutant mice are uniformly susceptible, The in fected mutant mice developed a significantly stronger Th1 type of immu ne response than the wild-type or heterozygous mice, The mutant mice s howed reduced nonspecific inflammatory response to carrageenin, and we re resistant to lipopolysaccharide-induced mortality.