INVOLVEMENT OF VARIOUS COMBINATIONS OF ENDOGENOUS INFLAMMATORY CYTOKINES IN LISTERIA MONOCYTOGENES-INDUCED EXPRESSION OF INDUCIBLE NITRIC-OXIDE SYNTHASE IN MICE

Using an in vitro infection of spleen cells with Listeria monocytogene s, the relationship between endogenous cytokines and the expression of inducible nitric oxide synthase (iNOS) was examined. When all interfe ron (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 reduc tion of iNOS expression and nitrite production in culture. However, th ere was no reduction of iNOS expression and nitrite production when th ese cytokines were individually neutralized. After the depletion of na tural 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 k iller cell-depleted culture resulted in the reduction of iNOS expressi on. Thus, various combinations of cytokines appeared to play an import ant role in iNOS induction by L. monocytogenes.