title: The role of adrenal gland microenvironment in the HPA axis function and dysfunction during sepsis.
abstract: Sepsis and septic shock in response to bacterial or viral infections remain the major health problem worldwide. Despite decades of intensive research and improvements in medical care, severe sepsis is associated with high mortality. Rapid activation of the adrenal gland glucocorticoid and catecholamine production is a fundamental component of the stress response and is essential for survival of the host. However, in many critically ill patients this homeostatic function of the adrenal gland is often impaired. In these patients, plasma levels of adrenocorticotropic hormone (ACTH) and cortisol are often dissociated. This has been attributed to the stimulatory action of non-ACTH factors within the adrenal gland such as cytokines, and recently with decreased cortisol metabolism and suppressed ACTH synthesis. Regulation of the hypothalamus-pituitary-adrenal (HPA) axis function during sepsis is a complex process which involves various immune and neuroendocrine interactions occurring at the levels of the central nervous system (CNS) and the adrenal gland. A coordinated interaction of numerous cell types and systems within the adrenal gland is involved in the sustained adrenal glucocorticoid production. This review article describes and discusses recent experimental findings regarding the role of adrenal gland microenvironment including the adrenal vasculature and the immune-adrenal crosstalk in the disregulated HPA axis during sepsis conditions. In summary, in addition to the reduced cortisol breakdown and related ACTH suppression, sepsis-mediated chronic activation of the immune-adrenal crosstalk and vascular dysfunction may contribute to the HPA axis dysregulation found in septic patients.
authors.affiliation: Department of Medicine III, Faculty of Medicine of the Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. Electronic address: waldemar.kanczkowski@uniklinikum-dresden.de.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Kanczkowski
authors.affiliation: Department of Medicine III, Faculty of Medicine of the Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
authors.forename: Mariko
authors.initials: M
authors.lastname: Sue
authors.affiliation: Clinic of Anesthesiology, Intensive Care Medicine and Pain Therapy, 60595 Frankfurt am Main, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Zacharowski
authors.affiliation: Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, München, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Reincke
authors.affiliation: Department of Medicine III, Faculty of Medicine of the Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Bornstein
mesh_terms: D000311:Adrenal Glands / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D060833:Cellular Microenvironment; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000473:pathology* / Q000503:physiopathology*; D010913:Pituitary-Adrenal System / Q000473:pathology* / Q000503:physiopathology*; D018805:Sepsis / Q000473:pathology / Q000503:physiopathology*; D013312:Stress, Physiological
keywords: Adrenal gland insufficiency; Del-1; Inflammation; Neutrophil-extracellular traps; The immune-adrenal crosstalk; Vasculature