SENSITIZATION TO LIPOPOLYSACCHARIDE IN MICE WITH ASYMPTOMATIC VIRAL-INFECTION - ROLE OF T-CELL-DEPENDENT PRODUCTION OF INTERFERON-GAMMA

The interplay between viral infection and lipopolysaccharide (LPS) was studied, Infection with a noncytopathogenic virus, lymphocytic chorio meningitis virus (LCMV), was found to sensitize mice to low doses of L PS. In vivo, this hypersensitivity correlated with hyperproduction of tumor necrosis factor-alpha (TNF-alpha), and in vitro, LPS-stimulated splenic adherent cells produced increased amounts of TNF-alpha. Hyperp roduction of TNF-alpha was temporally correlated with virus-induced pr oduction of interferon-gamma (IFN-gamma); only marginally increased IF N-gamma and TNF-alpha production was observed in LCMV-infected, T cell -deficient mice and in mice infected with vesicular stomatitis virus, a virus that induces much less T cell activation than does LCMV, Final ly, LCMV infection was much less efficient in priming IFN-gamma knocko ut mice for hyperproduction of TNF-alpha. These findings indicate that clinically silent viral infections may induce hypersensitivity to LPS through T cell activation and subsequent production of IFN-gamma; thi s sensitizes monocytes/macrophages for hyperproduction of TNF-alpha.