Toll-like receptor 4 plays a crucial role in the immune–adrenal response to systemic inflammatory response syndrome

Media type: E-Article
Title: Toll-like receptor 4 plays a crucial role in the immune–adrenal response to systemic inflammatory response syndrome
Contributor: Zacharowski, Kai; Zacharowski, Paula A.; Koch, Alexander; Baban, Aida; Tran, Nguyen; Berkels, Reinhard; Papewalis, Claudia; Schulze-Osthoff, Klaus; Knuefermann, Pascal; Zähringer, Ulrich; Schumann, Ralf R.; Rettori, Valeria; McCann, Samuel M.; Bornstein, Stefan R.
imprint: Proceedings of the National Academy of Sciences, 2006
Published in: Proceedings of the National Academy of Sciences
Language: English
DOI: 10.1073/pnas.0601527103
ISSN: 0027-8424; 1091-6490
Origination:
Footnote:
Description: <jats:p>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<jats:sup>−/−</jats:sup>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.</jats:p>
Access State: Open Access

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