ACQUIRED-RESISTANCE AGAINST A SECONDARY INFECTION WITH LISTERIA-MONOCYTOGENES IN MICE IS NOT DEPENDENT ON REACTIVE NITROGEN INTERMEDIATES

During an infection, inflammatory mediators can induce the production of nitric oxide, a reactive nitrogen intermediate (RNI) which plays a role in antimicrobial activity against a wide variety of pathogens. In vitro experiments have shown that release of RNI by macrophages is me diated by tumor necrosis factor alpha (TNF). Since TNF is essential fo r acquired resistance during a secondary Listeria monocytogenes infect ion in mice, the aim of the present study was to determine whether RNI are also involved in the course of such an infection. Mice which had recovered from a sublethal primary infection with 0.1 50% lethal dose of (LD(50)) L. monocytogenes were infected intravenously with 10 LD(50 ) of L. monocytogenes. During a primary infection, the number of bacte ria in the liver and spleen, as well as the concentration of RNI in pl asma, increased. During a secondary infection, the number of bacteria in the liver and spleen decreased whereas no significant increase in t he concentration of RNI in plasma was observed, Neutralization of endo genously produced TNF and gamma interferon by subcutaneous injection o f alginate-encapsulated monoclonal antibody-forming cells during a sec ondary infection resulted in an increase in the number of bacteria in the liver and spleen and an increase in the concentration of RNI in pl asma. When the production of RNI was inhibited by treatment of mice wi th the competitive NO-synthase inhibitor N-omega-nitro-L-arginine meth yl ester hydrochloride (L-NAME) and an L-arginine-deficient diet durin g a secondary infection, the proliferation of L, monocytogenes in the liver and spleen was not affected whereas the concentration of RNI in plasma of these mice was significantly reduced. Our findings that inhi bition of RNI formation during a secondary infection does not affect t he proliferation of L. monocytogenes in the liver and spleen and that enhanced elimination of bacteria from these organs is not accompanied by an increase in the concentration of RNI in plasma led to the conclu sion that resistance against a secondary infection with L. monocytogen es is not dependent on RNI.