title: Systemic immune challenge activates an intrinsically regulated local inflammatory circuit in the adrenal gland.
abstract: There is evidence from in vitro studies that inflammatory messengers influence the release of stress hormone via direct effects on the adrenal gland; however, the mechanisms underlying these effects in the intact organism are unknown. Here we demonstrate that systemic inflammation in rats elicited by iv injection of lipopolysaccharide results in dynamic changes in the adrenal immune cell population, implying a rapid depletion of dendritic cells in the inner cortical layer and the recruitment of immature cells to the outer layers. These changes are accompanied by an induced production of IL-1beta and IL-1 receptor type 1 as well as cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in these cells, implying local cytokine-mediated prostaglandin E(2) production in the adrenals, which also displayed prostaglandin E(2) receptors of subtypes 1 and 3 in the cortex and medulla. The IL-1beta expression was also induced by systemically administrated IL-1beta and was in both cases attenuated by IL-1 receptor antagonist, consistent with an autocrine signaling loop. IL-1beta similarly induced expression of cyclooxygenase-2, but the cyclooxygenase-2 expression was, in contrast, further enhanced by IL-1 receptor antagonist. These data demonstrate a mechanism by which systemic inflammatory agents activate an intrinsically regulated local signaling circuit that may influence the adrenals' response to immune stress and may help explain the dissociation between plasma levels of ACTH and corticosteroids during chronic immune perturbations.
authors.affiliation: Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Engström
authors.forename: Khadijah
authors.initials: K
authors.lastname: Rosén
authors.forename: Anna
authors.initials: A
authors.lastname: Angel
authors.forename: Anna
authors.initials: A
authors.lastname: Fyrberg
authors.forename: Ludmila
authors.initials: L
authors.lastname: Mackerlova
authors.forename: Jan Pieter
authors.initials: JP
authors.lastname: Konsman
authors.forename: David
authors.initials: D
authors.lastname: Engblom
authors.forename: Anders
authors.initials: A
authors.lastname: Blomqvist
mesh_terms: D000311:Adrenal Glands / Q000502:physiology*; D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics; D003713:Dendritic Cells / Q000502:physiology; D005786:Gene Expression Regulation; D007107:Immune System / Q000502:physiology*; D007249:Inflammation / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics; D019746:Intramolecular Oxidoreductases / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000502:physiology; D008297:Male; D000071876:Prostaglandin-E Synthases; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000235:genetics; D015398:Signal Transduction
chemical_list: D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases