Effect of Bacterial Endotoxin on Resistance of Mice to Viral Encephalitides

Abstract

Summary Purified endotoxin prepared from Salmonella abortus equi enhanced the resistance of mice to infection with the viruses of eastern equine encephalomyelitis (EEE) and encephalomyocarditis (EMC). The protective effects were manifested by a moderate reduction in incidence of death and slight, but definite, prolongation of survival time. Increased resistance could be demonstrated in infections initiated by either the intracerebral or intraperitoneal route. A single dose of endotoxin administered i.p., i.v. or i.c. 24 hours before challenge was often effective. However, combined i.p. and i.c. injections of endotoxin further augmented resistance to i.p. infection with EEE or EMC virus, and the most pronounced effect was evident in mice given repeated i.p. doses of endotoxin. In contrast to previous studies of “nonspecific” resistance to bacterial infection or viral toxicity, a favorable outcome was also demonstrable when endotoxin was administered concomitantly with challenge virus or when a course of treatment was begun 6 hr after i.p. infection with EEE virus. Endotoxin-induced resistance to the lethal action of EEE virus was accompanied by moderate inhibition of virus multiplication in brain. Endotoxin had no effect on multiplication of EEE virus in tissue culture, nor could it be shown to stimulate the production of an antiviral substance in brain. Certain differences were noted between endotoxin-induced resistance to viral encephalitis and the viral interference phenomenon. Intracerebral injection of influenza virus caused striking resistance to infection with EEE virus and marked inhibition of virus multiplication in brain. Although the capacity of influenza virus to protect mice against infection with EMC virus was slightly greater than that of bacterial endotoxin, no effect could be demonstrated unless the interfering virus was injected directly into the brain. Unlike bacterial endotoxin, influenza virus effectively suppressed multiplication of EEE virus in tissue cultures of chicken embryo fibroblasts.