Effect of 5-lipoxygenase inhibitor against lipopolysaccharide-induced hypothermia in mice

Abstract

Bacterial endotoxin produces sepsis associated with alterations in body temperature (fever or hypothermia). The intraperitoneal administration of bacterial endotoxin, lipopolysaccharide (LPS; 50 μg/mouse) led to a decrease in colonic temperature starting 1 hr after the injection. The hypothermic effect was accompanied by a significant increase in hypothalamic leukotriene B₄ (LTB₄) and prostaglandin E₂ (PGE₂) levels. 5-lipoxygenase inhibitor, zileuton (200 and 400 Mg/kg. po) administered 30 min before LPS challenge significantly prevented hypothermia. However, non-selective cyclooxygenase inhibitor, indomethacin (10, 20 mg/kg, po) did not reverse the hypothermic response. Further, pretreatment of mice with zileuton prevented LPS-stimulated increase in hypothalamic LTB₄ levels and caused a relatively small increase in PGEz levels. Indomethacin had no effect on LTB₄ levels but it reduced PGE₂ levels. These results suggest a possible involvement of leukotrienes in LPS-induced hypothermia and the potential protective role of 5-lipoxygenase inhibitors in endotoxemia.