Involvement of various combinations of endogenous inflammatory cytokines in Listeria monocytogenes-induced expression of inducible nitric oxide synthase in mice.

Using a in vitro infection of spleen cells with Listeria monocytogenes, the relationship between endogenous cytokines and the expression of inducible nitric oxide synthase (iNOS) was examined. When all interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 alpha, or the combination of IFN-gamma with either TNF-alpha or IL-1 alpha were neutralized by antibodies, there was a significant reduction of iNOS expression and nitrite production in culture. However, there was no reduction of iNOS expression and nitrite production when these cytokines were individually neutralized. After the depletion of natural killer cells, there was no change in the expression of Listeria-induced iNOS and nitrite production although the IFN-gamma production was abrogated. Neutralization of TNF-alpha and IL-1 alpha in natural killer cell-depleted culture resulted in the reduction of iNOS expression. Thus, various combinations of cytokines to play an important role in iNOS induction by L. monocytogenes.