Characterization of the hypothermic component of LPS-induced dual thermoregulatory response in rats

We have previously shown that Escherichia coli O111:B4 serotype lipopolysaccharide (LPS) produced a dual change in rectal temperature (Tb), in which hypothermia preceded fever at subthermoneutral ambient temperature (Tamb; 24-26 degrees C) in rats. In this study, the characteristics of the initial hypothermic response were evaluated. Hypothermia was significant when LPS (50 microg/kg, i.p.) was injected at thermoneutral Tamb (30 degrees C). There was no heat loss through tail skin during hypothermia. The open field activity of the rats did not change during this period. However, serum levels of tumor necrosis factor-alpha (TNF-alpha) elevated at the beginning of the hypothermia, whereas serum levels of interleukin (IL)-1beta and interferon (IFN)-gamma remained unchanged. A nonselective cyclooxygenase inhibitor (indomethacin, 5 mg/kg, s.c.) inhibited hypothermia and serum TNF-alpha elevation, which resulted in an acceleration of the subsequent pyrogenic response. Moreover, a nonselective inhibitor of nitric oxide synthase (nitro L-arginine methyl ester (L-NAME), 10 mg/kg, s.c.) not only abolished fever but also prolonged the initial hypothermic response. These data suggest that the hypothermic component of low dose LPS-induced dual response is a regulated decrease in Tb. The data also suggest that hypothermia and fever may occur independently as two different thermoregulatory strategies against immune challenge in rats.