Involvement of inflammatory cytokines and nitric oxide in the expression of non-specific resistance to Listeria monocytogenes in mice induced by viable but not killed Mycobacterium bovis BCG.

The non-specific defense against Listeria monocytogenes could be induced by viable BCG but not by killed BCG in mice. In order to understand the mechanism of antilisterial activity, viable and killed BCG were compared for their ability of inducing cytokine gene expression in spleen cells. Both viable and killed BCG induced the same level of mRNA expression of interleukin 10 (IL-10), transforming growth factor beta (TGF-beta), IL-12 and tumor necrosis factor alpha (TNF-alpha). Gene expression and production of IL-1 alpha and gamma interferon (IFN-gamma) could be induced by stimulation only with viable BCG. Viable BCG but not killed BCG induced the mRNA expression of inducible nitric oxide synthase (iNOS). Treatment of mice with NG-monomethyl-L-arginine acetate (NMMA) significantly impaired the non-specific antilisterial action induced by viable BCG. These results demonstrated that NO is an important mediator for the non-specific antilisterial activity induced by viable BCG, and IFN-gamma, IL-1 alpha and TNF-alpha may play a critical role in the non-specific antilisterial activity.