title: Female Sex Hormones Influence the Febrile Response Induced by Lipopolysaccharide, Cytokines and Prostaglandins but not by Interleukin-1β in Rats.
abstract: There are differences in the immune response, and particularly fever, between males and females. In the present study, we investigated how the febrile responses induced by lipopolysaccharide (LPS) and different endogenous pyrogens were affected by female gonadal hormones. The febrile response to i.p. injection of LPS (50 μg/kg) was 40% lower in female rats compared to male or ovariectomised (OVX) female rats. Accordingly, oestrogen replacement in OVX animals reduced LPS-induced fever. Treatment with the prostaglandin synthesis inhibitor indomethacin (2 mg/kg, i.p. 30 min before) reduced the febrile response induced by LPS in both OVX (88%) and sham-operated (71%) rats. In line with the enhanced fever in OVX rats, there was increased expression of cyclooxygenase-2 (COX-2) in the hypothalamus and elevated levels of prostaglandin E2(PGE2). In addition, OVX rats were hyper-responsive to PGE2injected i.c.v. By contrast to the enhanced fever in response to LPS and PGE2, the febrile response induced by i.c.v. injection of interleukin (IL)-1β was unaffected by ovariectomy, whereas the responses induced by tumour necrosis factor (TNF)-α and macrophage inflammatory protein (MIP)-1α were completely abrogated. These results suggest that the mediators involved in the febrile response in females are similar to males, although the reduction of female hormones may decrease the responsiveness of some mediators such as TNF-α and MIP-1α. Compensatory mechanisms may be activated in females after ovariectomy such as an augmented synthesis of COX-2 and PGE2.
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Curitiba, Brazil.
authors.forename: H O
authors.initials: HO
authors.lastname: Brito
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Curitiba, Brazil.
authors.forename: D R
authors.initials: DR
authors.lastname: Radulski
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: D B
authors.initials: DB
authors.lastname: Wilhelms
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Stojakovic
authors.affiliation: Department of Medicine III, Federal University of Maranhão, São Luís, Brazil.
authors.forename: L M O
authors.initials: LM
authors.lastname: Brito
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: D
authors.initials: D
authors.lastname: Engblom
authors.affiliation: Department of Cell Biology, Federal University of Paraná, Curitiba, Brazil.
authors.forename: C R C
authors.initials: CR
authors.lastname: Franco
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Curitiba, Brazil. aleksander@ufpr.br.
authors.forename: A R
authors.initials: AR
authors.lastname: Zampronio
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D004967:Estrogens / Q000008:administration & dosage / Q000502:physiology; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000378:metabolism*; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D007213:Indomethacin / Q000008:administration & dosage; D053583:Interleukin-1beta / Q000378:metabolism*; D008070:Lipopolysaccharides; D008297:Male; D010052:Ovariectomy; D011448:Prostaglandin Antagonists / Q000008:administration & dosage; D011453:Prostaglandins / Q000378:metabolism*; D017208:Rats, Wistar; D012727:Sex Characteristics
chemical_list: D016207:Cytokines; D004967:Estrogens; D012739:Gonadal Steroid Hormones; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D007213:Indomethacin
keywords: fever; macrophage-inflammatory protein-1α; oestrogen; tumour necrosis factor-α