Nitric oxide is protective in listeric meningoencephalitis of rats

The bacterium Listeria monocytogenes causes meningoencephalitis in humans. In rodents, listeriosis is associated with granulomatous lesions in the liv er and the spleen, but not with meningoencephalitis, were, infant rats were infected intracisternally to generate experimental listeric meningoencepha litis. Dose-dependent effects of intracisternal inoculation with L. monocyt ogenes on survival and activity were noted; 10(4) L. monocytogenes organism s induced a self-limiting brain infection. Bacteria invaded the basal menin ges, chorioid plexus and ependyme, spread to subependymal tissue and hippoc ampus, and disappeared by day 7. This was paralleled by recruitment and sub sequent disappearance of macrophages expressing inducible nitric oxide synt hase (iNOS) and nitrotyrosine accumulation, an indication of nitric oxide ( NO.) production. Treatment with the spin-trapping agent alpha -phenyl-tert- butyl nitrone (PBN) dramatically increased mortality and led to bacterial n umbers in the brain 2 orders of magnitude higher than in control animals. T reatment with the selective iNOS inhibitor L-N-6-(1-iminoethyl)-lysine (L-N IL) increased mortality to a similar extent and led to 1 order of magnitude higher bacterial counts in the brain, compared with controls, The numbers of bacteria that spread to the spleen and liver did not significantly diffe r among L-NIL-treated, PEN-treated, and control animals. Thus, the infant r at brain is able to mobilize powerful antilisterial mechanisms, and both re active oxygen and NO. contribute to Listeria growth control.