Influenza virus-induced encephalopathy in mice: interferon production and natural killer cell activity during acute infection.

Mice injected intracerebrally with infectious influenza virus (60 hemagglutinin units) developed lethargy, seizures, comas, and died 2 to 5 days postinfection. As early as 6 h after infection, the cerebrospinal fluid (CSF) in these animals was infiltrated with polymorphonuclear cells, mononuclear leukocytes, and large granular lymphocytes. Potent natural killer (NK) cell activity was observed for both CSF and spleen cell populations over the same period. This NK cell activity correlated with interferon (IFN) levels in the CSF and serum. Treatment of lethally infected mice with either anti-IFN alpha-IFN beta or anti-ganglio-n-tetraoglyceramide antiserum ameliorated the disease, reduced mortality, and effected changes in the relative proportions of inflammatory cell populations infiltrating the CSF. The possible significance of IFN and NK cell activity in the development of this influenza virus-induced encephalopathy is discussed.