PMID- 10381603 OWN - NLM STAT- MEDLINE DCOM- 19991020 LR - 20240317 IS - 0022-3751 (Print) IS - 1469-7793 (Electronic) IS - 0022-3751 (Linking) VI - 518 ( Pt 2) IP - Pt 2 DP - 1999 Jul 15 TI - Brain sites of action of endogenous interleukin-1 in the febrile response to localized inflammation in the rat. PG - 585-94 AB - 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 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. FAU - Cartmell, T AU - Cartmell T AD - School of Biological Sciences, University of Manchester, Manchester M13 9PT, UK. FAU - Luheshi, G N AU - Luheshi GN FAU - Rothwell, N J AU - Rothwell NJ LA - eng GR - WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Physiol JT - The Journal of physiology JID - 0266262 RN - 0 (Interleukin-1) RN - 0 (Lipopolysaccharides) RN - 0 (Receptors, Interleukin-1) SB - IM MH - Animals MH - Body Temperature/drug effects MH - Brain/*anatomy & histology MH - Brain Chemistry/*physiology MH - Dose-Response Relationship, Drug MH - Fever/*physiopathology MH - Hypothalamus/anatomy & histology/drug effects MH - Inflammation/*physiopathology MH - Injections, Intraventricular MH - Interleukin-1/*physiology MH - Lipopolysaccharides/pharmacology MH - Male MH - Microinjections MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Interleukin-1/antagonists & inhibitors PMC - PMC2269440 EDAT- 1999/06/25 00:00 MHDA- 1999/06/25 00:01 PMCR- 2000/07/15 CRDT- 1999/06/25 00:00 PHST- 1999/06/25 00:00 [pubmed] PHST- 1999/06/25 00:01 [medline] PHST- 1999/06/25 00:00 [entrez] PHST- 2000/07/15 00:00 [pmc-release] AID - PHY_9044 [pii] AID - 10.1111/j.1469-7793.1999.0585p.x [doi] PST - ppublish SO - J Physiol. 1999 Jul 15;518 ( Pt 2)(Pt 2):585-94. doi: 10.1111/j.1469-7793.1999.0585p.x.