PMID- 23500835 OWN - NLM STAT- MEDLINE DCOM- 20140207 LR - 20130517 IS - 1873-1686 (Electronic) IS - 0167-0115 (Linking) VI - 184 DP - 2013 Jun 10 TI - Antipyretic effect of central [Pyr1]apelin13 on LPS-induced fever in the rat. PG - 6-13 LID - S0167-0115(13)00047-5 [pii] LID - 10.1016/j.regpep.2013.03.018 [doi] AB - Intracerebroventricular (i.c.v.) injections of apelins have been shown to modulate the central control of cardiovascular function, as well as the homeostasis of fluid and salt balance, and to some extent also body core temperature. Here, we investigated the effects of i.c.v. administration of [Pyr(1)]apelin13 (PyrAp13; 20nmol) dissolved in artificial cerebrospinal fluid (aCSF), as compared to aCSF alone, on fever and sickness behavior elicited in rats by intraperitoneal injection of bacterial lipopolysaccharide (LPS, 100 mug/kg). Injections of LPS induced a short phase of hypothermia followed by a biphasic fever, depression of motor activity, anorexia and adipsia. I.c.v. injections of PyrAp13 without systemic LPS application slightly augmented motor activity at statistically unaltered core temperature. In combination with LPS, central administration of PyrAp13 significantly reduced fever during the time period of 3-9h after injection, but did not significantly attenuate anorexia and adipsia, and had no effect on LPS-induced lethargy. Rats injected with PyrAp13 along with LPS showed a reduced level of LPS-induced circulating tumor necrosis factor-alpha (TNF-alpha). Primary neuroglial cultures established from the hypothalamic paraventricular nucleus (PVN) and the median preoptic nucleus (MnPO), brain sites being of major importance for central thermoregulation and also expressing the apelin receptor, were incubated with medium alone, medium containing LPS (100 mug/ml) or LPS plus PyrAp13 (10(-6) mol/L). Ninety minutes after start of the incubation, LPS alone but not LPS in combination with PyrAp13 (10(-6) mol/L) caused a significant elevation of TNF-alpha in the supernatants. The novel observation that PyrAp13 represents a centrally acting endogenous antipyretic peptide is discussed in relation to its capacity to modulate peripheral and central formation of TNF-alpha. CI - Copyright (c) 2013 Elsevier B.V. All rights reserved. FAU - Hatzelmann, Thomas AU - Hatzelmann T AD - Institut fur Veterinar-Physiologie und -Biochemie, Justus-Liebig-Universitat Giessen, Giessen, Germany. FAU - Harden, Lois M AU - Harden LM FAU - Roth, Joachim AU - Roth J FAU - Gerstberger, Rudiger AU - Gerstberger R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130314 PL - Netherlands TA - Regul Pept JT - Regulatory peptides JID - 8100479 RN - 0 (Antipyretics) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Lipopolysaccharides) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (apelin 13, Pyr(1)-) SB - IM MH - Animals MH - Antipyretics/*pharmacology/therapeutic use MH - Fever/*drug therapy/metabolism/physiopathology MH - Injections, Intraperitoneal MH - Intercellular Signaling Peptides and Proteins/*pharmacology/therapeutic use MH - Lipopolysaccharides/*pharmacology MH - Male MH - Paraventricular Hypothalamic Nucleus/metabolism MH - Rats MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 2013/03/19 06:00 MHDA- 2014/02/08 06:00 CRDT- 2013/03/19 06:00 PHST- 2012/08/20 00:00 [received] PHST- 2013/01/15 00:00 [revised] PHST- 2013/03/03 00:00 [accepted] PHST- 2013/03/19 06:00 [entrez] PHST- 2013/03/19 06:00 [pubmed] PHST- 2014/02/08 06:00 [medline] AID - S0167-0115(13)00047-5 [pii] AID - 10.1016/j.regpep.2013.03.018 [doi] PST - ppublish SO - Regul Pept. 2013 Jun 10;184:6-13. doi: 10.1016/j.regpep.2013.03.018. Epub 2013 Mar 14.