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Am J Physiol Regul Integr Comp Physiol 292: R1846-R1850, 2007. First published February 1, 2007; doi:10.1152/ajpregu.00786.2006
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INFLAMMATION AND CYTOKINES

Escherichia coli lipopolysaccharides produce serotype-specific hypothermic response in biotelemetered rats

Eyup S. Akarsu and Soner Mamuk

Ankara University, School of Medicine, Department of Pharmacology and Clinical Pharmacology, Sihhiye, Ankara, Turkey

Submitted 10 November 2006 ; accepted in final form 26 January 2007

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 µg/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.

acute-phase response; fever; endotoxin; antipyretic cytokines; cyclooxygenase-1 selective inhibitors



Address for reprint requests and other correspondence: E. S. Akarsu, Ankara Univ., School of Medicine, Dept. of Pharmacology and Clinical Pharmacology, Sihhiye, 06100, Ankara, Turkey (e-mail address: akarsu{at}dialup.ankara.edu.tr)




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Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
A. A. Steiner, J. C. Hunter, S. M. Phipps, T. B. Nucci, D. L. Oliveira, J. L. Roberts, A. C. Scheck, D. L. Simmons, and A. A. Romanovsky
Cyclooxygenase-1 or -2--which one mediates lipopolysaccharide-induced hypothermia?
Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2009; 297(2): R485 - R494.
[Abstract] [Full Text] [PDF]




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