title: Sex difference in link between interleukin-6 and stress.
abstract: Inflammation contributes to disease development, and the neuroimmunoendocrine interface is a potential site of action for inflammatory products like IL-6 to affect health. Although plasma IL-6 can stimulate the activity of the hypothalamo-pituitary-adrenocortical (HPA) axis, the precise role, if any, for IL-6 in the HPA response to nonimmunological stressors is unclear. The purpose of this study was to test the hypothesis that IL-6 in the stalk median eminence (SME) can be directly involved in stimulating ACTH secretion in response to acute stress in female swine. This study was undertaken as a result of finding IL-6 localized to the external zone of the SME next to the hypophyseal portal vessels. Results indicate that content of IL-6 in the SME decreases in response to acute stress along with an increase in nuclear phosphorylated signal transducer and activator of transcription-3 (pSTAT-3) in pituitary corticotrophs and a simultaneous increase in plasma concentrations of IL-6 and ACTH. Furthermore, we show that females concomitantly display greater SME content of IL-6 and greater HPA responsiveness to stress, thereby suggesting that IL-6 release from the SME is an integral factor contributing to enhanced stress responsiveness in females. Our results provide evidence for a direct link between IL-6 and ACTH release and reveal a sex difference in this relationship.
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, Missouri 65211, USA. ryan.jankord@uc.edu
authors.forename: Ryan
authors.initials: R
authors.lastname: Jankord
authors.forename: James R
authors.initials: JR
authors.lastname: Turk
authors.forename: James C
authors.initials: JC
authors.lastname: Schadt
authors.forename: Jennifer
authors.initials: J
authors.lastname: Casati
authors.forename: Venkataseshu K
authors.initials: VK
authors.lastname: Ganjam
authors.forename: Elmer M
authors.initials: EM
authors.lastname: Price
authors.forename: Duane H
authors.initials: DH
authors.lastname: Keisler
authors.forename: M Harold
authors.initials: MH
authors.lastname: Laughlin
mesh_terms: D000208:Acute Disease; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008473:Median Eminence / Q000378:metabolism*; D005082:Physical Exertion; D010913:Pituitary-Adrenal System / Q000502:physiology; D012149:Restraint, Physical; D012727:Sex Characteristics; D013312:Stress, Physiological / Q000378:metabolism* / Q000503:physiopathology*; D013552:Swine; D013556:Swine, Miniature
chemical_list: D015850:Interleukin-6; D000324:Adrenocorticotropic Hormone