1150-1155Bacterial 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