salicylates and Hypothermia

We investigated whether LPS-induced hypothermia develops in a serotype-specific manner in biotelemetered conscious rats. Two different Escherichia coli serotypes of LPSs were injected at a dose of 250 mug/kg ip. E. coli O55:B5 LPS elicited an initial hypothermia and subsequent fever, but E. coli O111:B4 LPS caused more potent monophasic hypothermia. Serum tumor necrosis factor (TNF)-alpha levels were dramatically elevated at the initial phase of the hypothermia induced by both LPSs. This elevation tended to subside at the nadir of E. coli O55:B5 LPS-induced response but progressively increased at the nadir of E. coli O111:B4 LPS hypothermia. Serum IL-10 levels were moderately elevated at the initial phase of the hypothermia and persisted at the same level at the nadir of each LPS-induced response. No change was observed at the serum IL-18 levels. A selective cyclooxygenase (COX)-1 enzyme inhibitor, valeryl salicylate (20 mg/kg sc), abolished the hypothermia without any effect on the elevated cytokine levels. Another COX-1-selective inhibitor, 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560; 1 mg/kg sc) inhibited hypothermic responses as well. Meanwhile, cytokine levels were also reduced by SC-560 treatment. These findings suggest that LPS-induced hypothermia may have serotype-specific characteristics in rats. E. coli O111:B4 LPS has more potent hypothermic activity than E. coli O55:B5 LPS; that may presumably be related to its higher or sustained capability to release antipyretic cytokines, such as TNF-alpha. COX-1 enzyme may be involved in the generation of the hypothermia, regardless of the type of LPS administered.

Topics: Animals; Cyclooxygenase Inhibitors; Escherichia coli; Hypothermia; Interleukin-10; Interleukin-18; Lipopolysaccharides; Male; Pyrazoles; Rats; Rats, Wistar; Salicylates; Telemetry; Tumor Necrosis Factor-alpha

The effects of selective cyclooxygenase-1 and cyclooxygenase-2 inhibitors (valeryl salicylate and SC-58236, respectively) on Escherichia coli O111:B4 lipopolysaccharide (LPS)-induced dual thermoregulatory changes and serum tumor necrosis factor-alpha elevation were investigated in rats. LPS (50 microg/kg, intraperitoneal) produced an initial hypothermia that was then followed by fever. Serum tumor necrosis factor-alpha levels elevated at the initial phase of hypothermia. Valeryl salicylate injections (20, 40, and 80 mg/kg, subcutaneous [s.c.]) completely inhibited hypothermia without any effect on the elevated serum tumor necrosis factor-alpha levels and on the subsequent fever. On the other hand, SC-58236 injections (10, 20, and 40 mg/kg, s.c.) only partially abolished the hypothermia. SC-58236 had no effect on the initiation of fever, however completely inhibited the maintenance of fever. The serum tumor necrosis factor-alpha elevation was not reduced by SC-58236 treatment. The combination of valeryl salicylate and SC-58236 also failed to inhibit the initiation of fever. These findings suggest that cycloxygenase-1 may have a predominant role for the development of LPS-induced hypothermia, but cyclooxygenase-1 does not seem to be involved in the mediation of LPS-induced fever. Meanwhile, cyclooxgenase-2 may be critical for the late phase rather than the initiation of the fever response in rats.

Topics: Animals; Body Temperature Regulation; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Cytokines; Fever; Hypothermia; Isoenzymes; Lipopolysaccharides; Male; Membrane Proteins; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Pyrazoles; Rats; Rats, Wistar; Salicylates; Sulfonamides; Tumor Necrosis Factor-alpha

The intraperitoneal administration of sodium salicylate, L-tryptophan, and tyrosine resulted in significant hypothermia when rats were exposed to a 4degree C ambient temperature. Salicylate and tryptophan increased plasma levels of nonprotein-bound tryptophan while total and bound tryptophan were reduced in salicylate-treated rats. Tryptophan concentrations were unaffected by tyrosine administration. Concomitant with increases in free plasma tryptophan, there occurred significant rises in brain levels of tryptophan in both groups of rats, while brain tyrosine levels were increased in those rats receiving tyrosine. Similarly, significant increments in hypothalamic serotonin levels in rats receiving salicylate or L-tryptophan and increases in hypothalamic norepinephrine in tyrosine-treated rats seem to reflect the increased availability of tryptophan and tyrosine for monamine synthesis. However, alternative mechanisms of hypothermiaseem to be operative since oxygen consumption studies demonstrate dissimilar results for tryptophan and salicylate administration.

Topics: Animals; Body Temperature Regulation; Brain; Environment, Controlled; Hypothalamus; Hypothermia; Injections, Intraperitoneal; Male; Norepinephrine; Rats; Salicylates; Serotonin; Tryptophan; Tyrosine