PROTECTIVE ROLE OF NITRIC-OXIDE IN STAPHYLOCOCCUS-AUREUS INFECTION INMICE

This study was carried out to determine the role of nitric oxide (NO) in Staphylococcus aureus infection in mice. NO production in spleen ce ll cultures was induced by heat-killed S. aureus. Expression of mRNA o f the inducible isoform of NO synthase (iNOS) was induced in the splee ns and kidneys of S. aureus-infected mice. When mice were treated with monoclonal antibodies (MAbs) against tumor necrosis factor alpha (TNF -alpha) or gamma interferon (IFN-gamma) before S. aureus infection, th e induction of iNOS mRNA expression in the kidneys was inhibited. Thes e MAbs also inhibited NO production in spleen cell cultures stimulated with heat-killed S. aureus. NO production in the spleen cell cultures and levels of urinary nitrate plus nitrite were suppressed by treatme nt with aminoguanidine (AG), a selective inhibitor of iNOS. The surviv al rates of AG treated mice were significantly decreased by either let hal or sublethal S. aureus infections. However, an effect of AG admini stration on bacterial growth was not observed in the spleens and kidne ys of mice during either type of infection. Production of TNF-alpha an d IFN-gamma was not affected by AG treatment in vitro and in vive. The se results suggest that NO plays an important role ire protection from lethality by the infection, but the protective role of NO in host res istance against S. aureus infection was not proved. Moreover, our resu lts show that TNF-alpha and IFN-gamma regulate NO production while NO may not be involved in the regulation of the production of these cytok ines during S. aureus infection.