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

Abstract

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-α) (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-α 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.