I Nunnally | PubMed Health

PubMed1994

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)

Animals↗

PubMed1993

Hyperthermia protects mice against the lethal effects of endotoxin.

Recently, investigators have reported that heat shock proteins (HSPs) can protect isolated cells from cytotoxicity induced by two important mediators of sepsis: interleukin-1 and tumor necrosis factor. The present study was undertaken to examine the hypothesis that transient whole body hyperthermia could decrease mortality from subsequent challenge with gram-negative endotoxin. We demonstrate that heat pretreatments improved long-term survival fivefold in a mouse endotoxin model and this was correlated with the production of HSPs. There was a marked difference in individual organ expression of the inducible 72-kDa heat shock protein (HSP72). Heat treatments caused significant HSP72 formation in lung, liver, kidney, and small intestine, but much lesser formation in heart, brain, and abdominal wall muscle. Additional experiments demonstrated that the protective effect of hyperthermic treatments against an endotoxin challenge occurred early, i.e., 1 and 2 h after heating, was maximal at 12 h, and had significantly diminished by 48 h. The formation and decay of HSP72 demonstrated a time course that paralleled the survival curve from endotoxin challenge, thus suggesting a possible role for HSP72 in the protective effect. Surprisingly, and in contrast to studies reported in incubated cells, endotoxin alone did not cause significant formation of HSP72 in vivo.

Anesthesia↗