Temperature-dependent modulation of lipopolysaccharide-induced interleukin-1β and tumor necrosis factor α expression in cultured human astroglial cells by dexamethasone and indomethacin

In bacterial meningitis, LPS induces production in cerebrospinal fluid of the cytokines IL-1β and tumor necrosis factor α (TNFα), which are the principle mediators of meningeal inflammation. IL-1β and TNFα induce fever, and elevated temperature may affect cytokine expression. Dexamethasone treatment improves outcome in bacterial meningitis possibly by inhibiting IL-1β and TNFα. In this report, the effects of elevated temperature and dexamethasone on LPS-stimulated IL-1β and TNFα mRNA gene expression and protein synthesis were studied in human astrocytoma cell lines and primary cultures of human fetal astrocytes. Cells cultured at 40°C exhibited smaller peaks of IL-1β and TNFα transcription and protein synthesis compared with cells cultured at 37°C. The addition of dexamethasone before, during, or after exposure of the cells to LPS resulted in temperature-dependent inhibition of IL-1β transcription and protein synthesis. The most extensive inhibition occurred in pretreated cells cultured at 37°C. Cotreatment with LPS and dexamethasone also inhibited TNFα mRNA transcription at both temperatures. The effects of another antiinflammatory agent, indomethacin, on LPS induction of IL-1β and TNFα mRNA were temperature and cell line dependent. These findings provide a possible explanation for the efficacy of dexamethasone treatment of bacterial meningitis and support the proposal that fever may be beneficial to the host in this disease.