Hypothermic response of mice to ornithine-containing lipids and to endotoxin

Abstract

The hypothermic response of mice to ornithine-containing lipids (Orn-Ls) of the form α-N-(3-acyloxyacyl)-ornithine and to endotoxin (Escherichia coli O111:B4 lipopolysaccharide [LPS]) was studied. After the administration of Orn-L or LPS to C3H/HeSlc mice, body temperature decreases were determined at 30-min intervals by inserting a thermistor into the rectum of each mouse. When Orn-L (750 μg) or LPS (70 μg) was injected into the mice, body temperature decreases of 0.8 and 2.0°C, respectively, occurred 1.8 to 2.0 h later. These body temperature decreases were completely suppressed by the preadministration of indomethacin. When anti-tumor necrosis factor alpha (TNF-α) antibody was administered before the administration of Orn-L or LPS, only the body temperature decrease by LPS was suppressed. The body temperature decrease by Orn-L was suppressed by anti-interleukin-1β (IL- 1β) antibody preadministration. Next, in order to study IL-1β and TNF-α mRNA expression in macrophages, peritoneal macrophages were collected 40 min after the administration of Orn-L or LPS to mice. The expression of IL-1β mRNA by stimulation with Orn-L was as strong as that by stimulation with LPS, but the expression of TNF-α mRNA by stimulation with Orn-L was very weak. Our previous studies of in vitro macrophage activation by Orn-L proved that strong induction of IL-1 and prostaglandin E2 generation by Orn-L occurred (Y. Kawai and K. Akagawa, Infect. Immun. 57:2086-2091, 1989). From these experiments, the weak body temperature decrease in mice caused by Orn-L was found to be mediated by cytokines different from those which mediate the strong body temperature decrease caused by LPS. Namely, it was caused by prostaglandin E2, being mediated by IL-1 but not by TNF-α.