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Research Article Free access | 10.1172/JCI115184

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

S Velasco, M Tarlow, K Olsen, J W Shay, G H McCracken Jr, and P D Nisen

Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063.

Find articles by Velasco, S. in: PubMed | Google Scholar

Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063.

Find articles by Tarlow, M. in: PubMed | Google Scholar

Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063.

Find articles by Olsen, K. in: PubMed | Google Scholar

Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063.

Find articles by Shay, J. in: PubMed | Google Scholar

Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063.

Find articles by McCracken, G. in: PubMed | Google Scholar

Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063.

Find articles by Nisen, P. in: PubMed | Google Scholar

Published May 1, 1991 - More info

Published in Volume 87, Issue 5 on May 1, 1991
J Clin Invest. 1991;87(5):1674–1680. https://doi.org/10.1172/JCI115184.
© 1991 The American Society for Clinical Investigation
Published May 1, 1991 - Version history
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Abstract

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

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