Hypothermia protects against endotoxin-induced acute lung injury in rats

Objective: Hypothermia in humans and animals is known to decrease the number and function of circulating neutrophils. Be-cause an activation of circulating neutrophils and their sequestration into the lung are important pathogenetic phenomena in endotoxin-associated lung injury, we conjectured that hypothermia could prevent this type of lung injury. Design and setting: Animal study at a university-affiliated research institute. Subjects: Thirty-six Sprague-Dawley rats. Interventions: After anesthesia, the rats were randomly assigned to normothermia (37degreesC, rectal temperature) or hypothermia (27degreesC), which was induced by surface cooling. After 1 h of stable temperature, the rats were administered intratracheal doses of lipopolysaccharide (LPS; 3 mg/kg) (normothermia-LPS; hypothermia-LPS) or an equivalent volume of normal saline (normothermia-saline; hypothermia-saline). The rectal temperature was maintained within PC of the target temperature for 6 h after the intratracheal treatment. Measurements and results: Compared with the normothermia-LPS group, the neutrophil count in bronchoalveolar lavage (BAL) fluid (p=0.002) and the myeloperoxidase activity of lung tissues (p=0.002) of the hypothermia-LPS group were both lower. Compared with the normothermiaLPS group, the BAL interleukin-1beta level of the hypothermia-LPS group was lower (p<0.001), whereas the BAL interleukin-10 level of the hypothermia-LPS group was higher (p=0.026). Compared with the normothermia-LPS group, the histologic scores for acute lung injury of the hypothermia-LPS group were lower (p=0.007). Conclusions: Hypothermia pretreatment decreased the pulmonary sequestration of neutrophils, induced a favorable balance between pro- and anti-inflammatory cytokines, and attenuated histologic injury in endotoxin-challenged rats.