The role of interleukin-18 in vesicular stomatitis virus infection of the CNS

Intranasal application of vesicular stomatitis virus (VSV) results in the i nitial infection of the olfactory receptor neurons and a rapid progression of the virus through the mouse central nervous system (CNS), Interleukin-18 (IL-18) is an 18,3-kd cytokine that induces interferon gamma (IFN-gamma) p roduction in mice. IL-18 is synthesized as an inactive precursor that is cl eaved and activated by caspase-1/interleukin-1 beta converting enzyme (ICE) , IL-18 shares several biological properties with IL-12, including the abil ity to induce IFN-gamma production in T lymphocytes and natural killer (NK) cells. In the CNS, microglia and astrocytes produce IL-18 and IL-12, We ha ve previously shown that IL-12 promotes recovery from VSV encephalitis. Thi s led us to examine the potential role of IL-18 in the pathogenesis of VSV encephalitis. We show that both IL-18 and caspase-1 mRNA are consistently p resent in the CNS of mice, The addition of exogenous IL-18 to cell cultures does not affect the production of VSV, and addition of exogenous IL-18 at the time of infection does not alter the morbidity or mortality of BALB/c m ice. In vitro studies with neutralizing monoclonal antibody to IL-18 had no effect. From these results we conclude that in this system and under the e xperimental conditions used, unlike IL-12 and IFN-gamma, IL-18 does not pla y a significant role in the host response to VSV infection.