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 endotoxem ia markedly increase survival. A potential mechanism for the beneficia l effect of heat could be effects on IL-1 alpha and TNF-alpha, importa nt mediators of sepsis and endotoxemia. Administration of IL-1 or TNF prior to development of sepsis and endotoxemia increases survival; thu s, 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 releas ed during sepsis or endotoxemia. Cells pretreated with heat do not pro duce as much IL-1 or TNF in response to endotoxin as cells that have n ot 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 anesthetize d 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 an esthesia and immersion, sham and heat-treated mice were injected with Escherichia coli endotoxin. Both heat-treated and sham mice had elevat ed plasma IL-1 alpha 2 h after anesthesia and immersion but IL-1 alpha was similar to 3-fold greater in the heated mice, 732 +/- 50 vs. 256 +/- 76 pg/ml (p < 0.01). Blood samples obtained after endotoxin reveal ed 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 v s. heated mice. We concluded that hyperthermia causes induction of IL- 1 alpha but not TNF-alpha and that increases in IL-1 alpha may be an i mportant mechanism for the beneficial effects of prophylactic heat tre atments on survival in sepsis and endotoxemia.