title: Toll-like receptor 4 plays a crucial role in the immune-adrenal response to systemic inflammatory response syndrome.
abstract: Sepsis and septic shock are leading killers in the noncoronary intensive care unit, and they remain worldwide health concerns. The initial host defense against bacterial infections involves Toll-like receptors (TLRs), which detect and respond to microbial ligands. In addition, a coordinated response of the adrenal and immune systems is crucial for survival during severe inflammation. Previously, we demonstrated a link between the innate immune system and the endocrine stress response involving TLR-2. Like TLR-2, TLR-4 is also expressed in human and mouse adrenals. In the present work, by using a low dose of LPS to mimic systemic inflammatory response syndrome, we have revealed marked cellular alterations in adrenocortical tissue and an impaired adrenal corticosterone response in TLR-4-/- mice. Our findings demonstrate that TLR-4 is a key mediator in the crosstalks between the innate immune system and the endocrine stress response. Furthermore, TLR polymorphisms could contribute to the underlying mechanisms of impaired adrenal stress response in patients with bacterial sepsis.
authors.affiliation: Molecular Cardioprotection and Inflammation Group, Department of Anesthesia, Heinrich Heine University, Dusseldorf 40225, Germany. kai.zacharowski@uni-duesseldorf.de
authors.forename: Kai
authors.initials: K
authors.lastname: Zacharowski
authors.forename: Paula A
authors.initials: PA
authors.lastname: Zacharowski
authors.forename: Alexander
authors.initials: A
authors.lastname: Koch
authors.forename: Aida
authors.initials: A
authors.lastname: Baban
authors.forename: Nguyen
authors.initials: N
authors.lastname: Tran
authors.forename: Reinhard
authors.initials: R
authors.lastname: Berkels
authors.forename: Claudia
authors.initials: C
authors.lastname: Papewalis
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulze-Osthoff
authors.forename: Pascal
authors.initials: P
authors.lastname: Knuefermann
authors.forename: Ulrich
authors.initials: U
authors.lastname: Zähringer
authors.forename: Ralf R
authors.initials: RR
authors.lastname: Schumann
authors.forename: Valeria
authors.initials: V
authors.lastname: Rettori
authors.forename: Samuel M
authors.initials: SM
authors.lastname: McCann
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Bornstein
mesh_terms: D000311:Adrenal Glands / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D003345:Corticosterone / Q000097:blood*; D016207:Cytokines / Q000097:blood*; D007113:Immunity, Innate / Q000235:genetics; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D016328:NF-kappa B / Q000378:metabolism; D018746:Systemic Inflammatory Response Syndrome / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000032:analysis / Q000235:genetics / Q000502:physiology*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone