ROLE OF CYTOKINES IN LIPOPOLYSACCHARIDE-INDUCED FUNCTIONAL AND STRUCTURAL ABNORMALITIES OF ASTROCYTES

The mechanism underlying meningitis-associated brain injury is unclear. This study investigated the hypothesis that lipopolysaccharide (LPS) alters astrocyte function and structure via the release of proinflammatory cytokines. In enriched murine astrocyte cultures, LPS inhibited (P < 0.05) glutamine synthetase activity, H-3-gamma aminobutyric acid uptake, and DNA synthesis; LPS also induced ultrastructural changes. Antibodies to tumor necrosis factor-alpha, interleukin-1, and interleukin-6 blocked (P < 0.05) in part the LPS-induced inhibition of astrocyte function. Also, treatment of astrocyte cultures with cytokines significantly altered these astrocyte functions and ultrastructure. Taken together, the present findings support the hypothesis that LPS affects astrocyte function and structure via the release of proinflammatory cytokines, especially tumor necrosis factor-alpha. 1994 Wiley-Liss, Inc.