AJP - Regulatory, Integrative and Comparative Physiology, Vol 266, Issue 1 1-R8, Copyright © 1994 by American Physiological Society

ARTICLES

Hypothermia to endotoxin involves reduced thermogenesis, macrophage-dependent mechanisms, and prostaglandins

R. H. Derijk, M. Van Kampen, N. Van Rooijen and F. Berkenbosch
Department of Pharmacology, Free University, Amsterdam, The Netherlands.

At a subthermoneutral ambient temperature of 24 degrees C, intravenous administration of bacterial endotoxin (lipopolysaccharide, LPS) to rats resulted in hypothermia associated with a fall in oxygen consumption followed by fever. At the thermoneutral ambient temperature of 30 degrees C, animals only responded to LPS with fever. The hypothermia and reduction in oxygen consumption were attenuated in rats with eliminated peripheral macrophages. By contrast, macrophage elimination did not affect the febrile response to LPS. Both the hypothermia and the febrile response to LPS were prevented by peripheral administration of the cyclooxygenase inhibitor indomethacin. We conclude that hypothermia in response to LPS is caused by reduced thermogenesis, involves antipyretic products released from peripheral macrophages, and is mediated by prostaglandins. In addition, the febrile response likewise involves prostaglandins, but in contrast to the hypothermia appears to be independent of pyrogens released from peripheral macrophages. Previously, we reported the induction of the pyrogen interleukin-1 in the brain during the time course of the febrile response to LPS (34). The latter observations support the hypothesis that the second phase of biphasic fever is mediated by synthesis and action of pyrogens inside the blood-brain barrier.

This article has been cited by other articles:

				E. S. Akarsu and S. Mamuk Escherichia coli lipopolysaccharides produce serotype-specific hypothermic response in biotelemetered rats Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2007; 292(5): R1846 - R1850. [Abstract] [Full Text] [PDF]

				A. Mouihate, T. F. Horn, and Q. J. Pittman Oxyresveratrol dampens neuroimmune responses in vivo: a selective effect on TNF-{alpha} Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2006; 291(5): R1215 - R1221. [Abstract] [Full Text] [PDF]

				A. Ledeboer, R. Binnekade, J. J. P. Breve, J. G. J. M. Bol, F. J. H. Tilders, and A.-M. Van Dam Site-specific modulation of LPS-induced fever and interleukin-1beta expression in rats by interleukin-10 Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2002; 282(6): R1762 - R1772. [Abstract] [Full Text] [PDF]

				K. Dokladny, A. Kozak, M. Wachulec, E. S. Wallen, M. G. Menache, W. Kozak, M. J. Kluger, and P. L. Moseley Effect of heat stress on LPS-induced febrile response in D-galactosamine-sensitized rats Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2001; 280(2): R338 - R344. [Abstract] [Full Text] [PDF]

				A. Valles, O. Marti, A. Garcia, and A. Armario Single exposure to stressors causes long-lasting, stress-dependent reduction of food intake in rats Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2000; 279(3): R1138 - R1144. [Abstract] [Full Text] [PDF]

				T. Mizuno, Y. Kannan, M. Tokunaga, M. Moriyama, Y. Kiso, K. Kusakabe, J. Yamate, K. Kiyomiya, and T. Sugano Role of hypothermia induced by tumor necrosis factor on apoptosis and function of inflammatory neutrophils in mice Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2000; 278(1): R157 - R165. [Abstract] [Full Text] [PDF]

				L. Paul, V. Fraifeld, and J. Kaplanski Evidence supporting involvement of leukotrienes in LPS-induced hypothermia in mice Am J Physiol Regulatory Integrative Comp Physiol, January 1, 1999; 276(1): R52 - R58. [Abstract] [Full Text] [PDF]

				L. Kapas, M. K. Hansen, H.-Y. Chang, and J. M. Krueger Vagotomy attenuates but does not prevent the somnogenic and febrile effects of lipopolysaccharide in rats Am J Physiol Regulatory Integrative Comp Physiol, February 1, 1998; 274(2): R406 - R411. [Abstract] [Full Text] [PDF]