Effect of heat stress on LPS-induced febrile response in D-galactosamine-sensitized rats

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2001-02, Vol.280 (2), p.338-R344
• Main Authors: Dokladny, Karol, Kozak, Anna, Wachulec, Maciej, Wallen, Erik S, Menache, Margaret G, Kozak, Wieslaw, Kluger, Matthew J, Moseley, Pope L
• Format: Article
• Language: English
• Subjects: Animals; Fever - blood; Fever - chemically induced; Fever - physiopathology; Galactosamine - pharmacology; Hot Temperature; HSC70 Heat-Shock Proteins; HSP70 Heat-Shock Proteins - biosynthesis; Interleukin-6 - blood; Lipopolysaccharides - toxicity; Liver - drug effects; Liver - metabolism; Male; Rats; Rats, Sprague-Dawley; Stress, Physiological - physiopathology; Time Factors; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.2001.280.2.r338

1  Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque 87131; 2  Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87185; and 3  Department of Physiology and Endocrinology, Medical College of Georgia, Augusta, Georgia 30912 We have previously reported that heat conditioning augments lipopolysaccharide (LPS)-induced fever in rats, which is accompanied by an accumulation of heat shock protein (HSP) in the liver and the reduction of the plasma level of tumor necrosis factor (TNF- ) (Kluger MJ, Rudolph K, Soszynski D, Conn CA, Leon LR, Kozak W, Wallen ES, and Moseley PL. Am J Physiol Regulatory Integrative Comp Physiol 273: R858-R863, 1997). In the present study we have tested whether inhibition of protein synthesis in the liver can reduce the effect of this heat conditioning on the LPS-induced febrile response in the rat. D -galactosamine ( D -gal) was used to selectively inhibit liver protein synthesis. D -gal (500 mg/kg) or PBS as control was administered intraperitoneally 1 h before heat stress. LPS (50 µg/kg ip) was injected 24 h post-heat exposure. Treatment with D -gal blunted the febrile response to LPS. Moreover, heat-conditioned rats treated first with D -gal and subsequently with LPS demonstrated a profound fall in core temperature 10-18 h post-LPS. A significant increase of serum TNF- accompanied this effect of D -gal on fever. Heat-conditioned animals receiving D -gal showed an inhibition in inducible HSP-70 in the liver. These data support the role of hepatic function in modulating the febrile response to LPS. heat shock proteins; liver; heart; kidney; tumor necrosis factor- , interleukin-6, temperature regulation; fever; lipopolysaccharide