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


METHODS
Animal study in an institutional animal laboratory.


METHODS
Thirty-six Sprague-Dawley rats.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Induced hypothermia suppressed the release of inflammatory cytokine from alveolar macrophages and NF-kappaB activation in endotoxemic lung.
Lim
Chae-Man
CM
POB 145 Songpa, 138-600 Seoul, Korea. cmlim@amc.seoul.kr
Kim
Eun-Kyung
EK
Koh
Younsuck
Y
Kim
Woo-Sung
WS
Kim
Dong-Soon
DS
Kim
Won-Dong
WD
D000704:Analysis of Variance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D007036:Hypothermia, Induced; D007375:Interleukin-1 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000633:toxicity; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D016328:NF-kappa B / Q000096:biosynthesis*; D009504:Neutrophils / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha