Abstract

The interplay between viral infection and lipopolysaccharide (LPS) was studied. Infection with a noncytopathogenic virus, lymphocytic choriomeningitis virus (LCMV), was found to sensitize mice to low doses of LPS. In vivo, this hypersensitivity correlated with hyperproduction of tumor necrosis factor-α (TNF-α), and in vitro, LPS-stimulated splenic adherent cells produced increased amounts of TNF-α. Hyperproduction of TNF-α was temporally correlated with virus-induced production of interferon-γ (IFN-γ); only marginally increased IFN-γ and TNF-α 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. Finally, LCMV infection was much less efficient in priming IFN-γ knockout mice for hyperproduction of TNF-α. These findings indicate that clinically silent viral infections may induce hypersensitivity to LPS through T cell activation and subsequent production of IFN-γ; this sensitizes monocytes/macrophages for hyperproduction of TNF-α.

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