AJP - Endocrinology and Metabolism, Vol 256, Issue 1 E7-11, Copyright © 1989 by American Physiological Society

ARTICLES

Pyrogenic and thermogenic effects of interleukin 1 beta in the rat

M. J. Dascombe, N. J. Rothwell, B. O. Sagay and M. J. Stock
Department of Physiological Sciences, University of Manchester, United Kingdom.

Single injections of recombinant human interleukin 1 beta (IL-1 beta) caused large (up to 2 degrees C) and sustained (3 h) increases in body temperature in conscious rats. Intracerebroventricular injections (10-100 ng) were much more effective and elicited greater responses than intravenous injections (0.1-1 microgram). IL-1 beta increased resting oxygen consumption by 25-49% in a dose-dependent manner. The activity of the thermogenic proton conductance pathway in brown adipose tissue (BAT) mitochondria was assessed from purine nucleotide (GDP) binding and was elevated by 40 and 86% 1 h after intravenous (1 microgram) or intracerebroventricular (100 ng) injection of IL-1 beta, respectively. Regional tissue blood flow was determined in anesthetized rats from the distribution of radiolabeled microspheres. Blood flow to liver (hepatic arterial), testes, skin, and white adipose tissue was unaffected by IL-1 beta injection. Blood flow to brain and kidney was increased (142 and 50%) but reduced (58%) to skeletal muscle after intravenous but not intracerebroventricular injection of interleukin. In contrast, blood flow to BAT was markedly elevated after intravenous (288%) or intracerebroventricular (382%) injection of IL-1 beta. Severing the sympathetic nerves supplying the interscapular BAT depot prevented the increase in blood flow. These data indicate that the potent pyrogenic effects of IL-1 beta in the rat are due largely to a central action. Fever is associated with increases in metabolic rate and BAT activity, and these results provide support for the involvement of brown fat in thermogenesis associated with fever.

This article has been cited by other articles:

				H. Ashdown, S. Poole, P. Boksa, and G. N. Luheshi Interleukin-1 receptor antagonist as a modulator of gender differences in the febrile response to lipopolysaccharide in rats Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2007; 292(4): R1667 - R1674. [Abstract] [Full Text] [PDF]

				Y. Okamatsu-Ogura, N. Kitao, K. Kimura, and M. Saito Brown fat UCP1 is not involved in the febrile and thermogenic responses to IL-1beta in mice Am J Physiol Endocrinol Metab, April 1, 2007; 292(4): E1135 - E1139. [Abstract] [Full Text] [PDF]

				B. CANNON and J. NEDERGAARD Brown Adipose Tissue: Function and Physiological Significance Physiol Rev, January 1, 2004; 84(1): 277 - 359. [Abstract] [Full Text] [PDF]

				M. J. Kenney, F. Blecha, R. J. Fels, and D. A. Morgan Altered frequency responses of sympathetic nerve discharge bursts after IL-1beta and mild hypothermia J Appl Physiol, July 1, 2002; 93(1): 280 - 288. [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]

				C. A. Murray and M. A. Lynch Evidence That Increased Hippocampal Expression of the Cytokine Interleukin-1beta Is a Common Trigger for Age- and Stress-Induced Impairments in Long-Term Potentiation J. Neurosci., April 15, 1998; 18(8): 2974 - 2981. [Abstract] [Full Text] [PDF]