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 language | English (US) |
|---|---|
| Pages (from-to) | 1674-1680 |
| Number of pages | 7 |
| Journal | Journal of Clinical Investigation |
| Volume | 87 |
| Issue number | 5 |
| State | Published - May 1991 |
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Keywords
- Astrocytes
- Cytokines
- Endotoxin
- Fever
- Inflammation
ASJC Scopus subject areas
- Medicine(all)
Cite this
Temperature-dependent modulation of lipopolysaccharide-induced interleukin-1β and tumor necrosis factor α expression in cultured human astroglial cells by dexamethasone and indomethacin. / Velasco, Susana; Tarlow, Michael; Olsen, Kurt; Shay, Jerry W.; McCracken, George H.; Nisen, Perry D.
In: Journal of Clinical Investigation, Vol. 87, No. 5, 05.1991, p. 1674-1680.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Temperature-dependent modulation of lipopolysaccharide-induced interleukin-1β and tumor necrosis factor α expression in cultured human astroglial cells by dexamethasone and indomethacin
AU - Velasco, Susana
AU - Tarlow, Michael
AU - Olsen, Kurt
AU - Shay, Jerry W.
AU - McCracken, George H.
AU - Nisen, Perry D.
PY - 1991/5
Y1 - 1991/5
N2 - 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.
AB - 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.
KW - Astrocytes
KW - Cytokines
KW - Endotoxin
KW - Fever
KW - Inflammation
UR - http://www.scopus.com/inward/record.url?scp=0025806367&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025806367&partnerID=8YFLogxK
M3 - Article
VL - 87
SP - 1674
EP - 1680
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 5
ER -