Hyperthermia induces IL-1 alpha but does not decrease release of IL-1 alpha or TNF-alpha after endotoxin.
Heat treatments administered prior to the onset of sepsis or endotoxemia markedly increase survival. A potential mechanism for the beneficial effect of heat could be effects on IL-1 alpha and TNF-alpha, important mediators of sepsis and endotoxemia. Administration of IL-1 or TNF prior to development of sepsis and endotoxemia increases survival; thus, prophylactic heat treatments may protect by releasing IL-1 or TNF. Paradoxically, an alternative mechanism of protection of prophylactic heat treatments could be to decrease the amount of IL-1 and TNF released during sepsis or endotoxemia. Cells pretreated with heat do not produce as much IL-1 or TNF in response to endotoxin as cells that have not been pretreated with heat. The purpose of this investigation was to determine if hyperthermia caused release of cytokines and/or blunted the rise in cytokines occurring after endotoxin. Mice were anesthetized with ketamine/xylazine and immersed in a water bath at 37.0 or 42.0 degrees C for sham or heat treatments. At 6-7 h after recovery from anesthesia and immersion, sham and heat-treated mice were injected with Escherichia coli endotoxin. Both heat-treated and sham mice had elevated plasma IL-1 alpha 2 h after anesthesia and immersion but IL-1 alpha was approximately 3-fold greater in the heated mice, 732 +/- 50 vs. 256 +/- 76 pg/ml (p < 0.01). Blood samples obtained after endotoxin revealed no difference in levels of TNF-alpha (5477 +/- 742 vs. 6514 +/- 652 pg/ml) or IL-1 alpha (546 +/- 72 vs. 603 +/- 121 pg/ml) in the sham vs. heated mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110.
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D
Blake
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Bessey
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I
Karl
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I
Nunnally
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Hotchkiss
D000818:Animals; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D006979:Hyperthermia, Induced; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism; D008297:Male; D051379:Mice; D018805:Sepsis / Q000276:immunology / Q000517:prevention & control; D014115:Toxemia / Q000276:immunology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004731:Endotoxins; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; C044101:endotoxin, Escherichia coli