Toll-like receptor 4 plays a crucial role in the immune-adrenal response to systemic inflammatory response syndrome.
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.
Zacharowski
Kai
K
Molecular Cardioprotection and Inflammation Group, Department of Anesthesia, Heinrich Heine University, Dusseldorf 40225, Germany. kai.zacharowski@uni-duesseldorf.de
Zacharowski
Paula A
PA
Koch
Alexander
A
Baban
Aida
A
Tran
Nguyen
N
Berkels
Reinhard
R
Papewalis
Claudia
C
Schulze-Osthoff
Klaus
K
Knuefermann
Pascal
P
Zähringer
Ulrich
U
Schumann
Ralf R
RR
Rettori
Valeria
V
McCann
Samuel M
SM
Bornstein
Stefan R
SR
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*
D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone