Hypothermia inhibits cytokine release of alveolar macrophage and activation of nuclear factor kappaB in endotoxemic lung.

Abstract

We have previously reported that endotoxin-induced neutrophil infiltration of the lung is lower during hypothermia than during normothermia. Because neutrophil infiltration of the lung is considered a downstream phenomenon following an activation of tissue macrophages, we examined the effects of induced hypothermia on the proximal aspects of acute lung injury, which involves alveolar macrophages and nuclear transcription of cytokine genes. Animal study in an institutional animal laboratory. Thirty-six Sprague-Dawley rats. Rats were assigned to the following groups: normothermia (37 degrees C) with saline; hypothermia (27 degrees C) with saline; normothermia with lipopolysaccharide; hypothermia with lipopolysaccharide. After 1 h of stable temperature rats were intraperitoneally given lipopolysaccharide or an equivalent volume of normal saline. The temperature of rats was maintained within +/-1 degrees C of the target temperature for the subsequent 2 h, after which rats were subjected to lung lavage. Neutrophil count, TNF-alpha, and IL-1beta in lavage fluid were all higher with normothermia-LPS than in normothermia-saline. Neutrophil count, TNF-alpha, and IL-1beta levels of lavage fluid were lower with hypothermia-LPS than with normothermia-LPS. TNF-alpha release from cultured alveolar macrophages and NF-kappaB activity in lung tissue were both lower with hypothermia-LPS than with normothermia-LPS. I-kappaBalpha level in lung tissue was lower with normothermia-LPS than with the normothermia-saline, whereas I-kappaBalpha level in lung tissue did not differ between normothermia-saline and hypothermia-LPS. Induced hypothermia suppressed the release of inflammatory cytokine from alveolar macrophages and NF-kappaB activation in endotoxemic lung.