Abstract
We investigated the role played by inflammation in acute encephalitis following infection with a neurotropic virus by comparing the disease caused by the CVS strain of rabies virus in C57BL/6 and mice deficient for the p55 Kd TNF-α receptor (p55TNFR-/-). Morbidity (weight loss and paralysis) and mortality of infected mice were associated with viral propagation, cytokine (IL-6, IL-10, TNF-α and IFN-γ) production, induction of apoptosis and infiltration of inflammatory cells. Mortality occurred later in p55TNFR-/-(than in C57BL/6 mice. In contrast, morbidity and the number of cells undergoing apoptosis were similar in C57BL/6 and p55TNFR-/-mice.) This suggests that morbidity and mortality are independently regulated and that the death of the animal was not due to CNS apoptosis. Delayed mortality correlated with: a reduction in viral load on day 9 p.i., an increase in IFN-γ and IL-10 concentrations and a reduction in inflammatory cell infiltration in the CNS. Thus, these data indicate that CVS infection elicits an inflammatory response within the CNS and suggest that cytokines signaling via the p55 Kd TNF-α receptor is deleterious for the survival of the host. These results strongly suggest that, the modulation of TNF-α and up regulation of IFN-γ would be a powerful anti-virus strategy in cases of viral encephalitis.