PROTECTIVE EFFECT OF PICOLINIC-ACID ON MICE INTRACEREBRALLY INFECTED WITH LETHAL DOSES OF CANDIDA-ALBICANS

We have studied the effects of picolinic acid (PIA), a product of tryp tophan degradation, on mouse susceptibility to intracerebral infection with Candida albicans. We show that intraperitoneal administration of PLA significantly enhances the median survival time of mice inoculate d with the lethal challenge. Furthermore, intracerebral administration of this agent induces a protective state against the local lethal inf ection, the phenomenon depending upon the administration schedule and doses of PIA employed. According to survival data, yeast growth in the brain as well as yeast colonization of the kidneys are drastically re duced in PLA-treated mice compared with those for untreated controls. Northern (RNA) blot analysis of brain tissues demonstrates that mRNA l evels specific for tumor necrosis factor and interleukin 1 are augment ed and induced, respectively, after inoculation of PLA. These results indicate that PLA has a protective effect likely involving elicitation of a cytokine response in vivo against fungal infections.