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

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 microgram 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 microgram in 5 microliter) 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 microgram in 0.5 microliter 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 fie…