Resistance of interleukin-1 beta-deficient mice to fatal Sindbis virus encephalitis

Interleukin-1 beta (IL-1 beta) concentrations are frequently elevated in ce ntral nervous system (CNS) viral infections, but the pathophysiologic signi ficance of such elevations is not known. To examine the role of IL-1 beta i n CNS viral pathogenesis, we compared the natural histories of IL-1 beta-de ficient and mild-type 129 SV(ev) mice infected with a neurovirulent viral s train, neuroadapted Sindbis virus (NSV). We found that the incidence of sev ere paralysis and death was markedly decreased in NSV-infected IL-1 beta(-/ -) mice compared to NSV-infected wild-type mice (4 versus 88%, P < 0.001). Despite this marked difference in clinical outcome, no differences in numbe rs of apoptotic cells or presence of histopathologic lesions in the brains of moribund wild-type mice and those of clinically healthy IL-1 beta(-/-) m ice could be detected. These results suggest that IL-1 beta deficiency is p rotective against fatal Sindbis virus infection by a mechanism that does no t involve resistance to CNS virus-induced apoptosis or histopathology.