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

Susana Velasco, Michael Tarlow, Kurt Olsen, Jerry W. Shay, George H. McCracken, Perry D. Nisen

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1674-1680
Number of pages7
JournalJournal of Clinical Investigation
Volume87
Issue number5
DOIs
StatePublished - Jan 1 1991

Keywords

  • Astrocytes
  • Cytokines
  • Endotoxin
  • Fever
  • Inflammation

ASJC Scopus subject areas

  • Medicine(all)

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