Brain sites of action of endogenous interleukin‐1 in the febrile response to localized inflammation in the rat

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Abstract
1 Interleukin (IL)-1 is a potent endogenous pyrogen which causes fever when injected into a number of brain sites. However, the brain sites at which endogenous IL-1 acts to influence body temperature remain equivocal. The aim of this study was to determine the effect of local administration of the interleukin-1 receptor antagonist (IL-1ra) into specific sites in the hypothalamus, and other brain regions known to contain receptors for IL-1, on the febrile response of rats to peripheral injection of lipopolysaccharide (LPS) into a subcutaneous air pouch (intrapouch, i.p.o.) that does not lead to LPS appearance in the circulation. 2 Injection of LPS (100 μg kg−1, i.p.o.) induced a rise in body temperature which commenced 1·5 h after injection and was maximal at 3 h (38·9 ± 0·2 °C, compared with 37·0 ± 0·1 °C at 0 h, n= 6, P < 0·001). Intracerebroventricular (i.c.v.) IL-1ra (500 μg in 5 μl) significantly attenuated LPS fever (IL-1ra, 37·7 ± 0·2 °C; saline, 38·9 ± 0·2 °C; n= 6, P < 0·001). Unilateral microinjection of IL-1ra (50 μg in 0·5 μl at 0 + 1 h) into the anterior hypothalamus (AH), paraventricular hypothalamic nucleus (PVH), peri-subfornical organ, subfornical organ (SFO) or hippocampus (dentate gyrus and CA3 region) also significantly reduced the fever induced by LPS. 3 The same dose of IL-1ra had no effect on fever when administered into the ventromedial hypothalamus (VMH), organum vasculosum lamina terminalis (OVLT), CA1 field of the hippocampus, striatum or cortex. 4 These data indicate that the action of endogenous IL-1 in the brain during fever is site specific, acting at the AH, PVH, SFO and hippocampus, but not the VMH, OVLT and striatum or cortex.

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