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

PAULA A. ZACHAROWSKI; ALEXANDER KOCH,; AIDA BABAN; NGUYEN TRAN; REINHARD BERKELS; CLAUDIA PAPEWALIS; KLAUS SCHULZE-OSTHOFF; PASCAL KNUEFERMANN; ULRICH ZAHRINGER; RALF R. SCHUMANN; VALERIA BESUHLI DE RETTORI; SAMUEL M. MCCANN; STEFAN R. BORNSTEIN

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Año: 2006 vol. 103 p. 6392 - 6397

0027-8424

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 Tolllike 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
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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. bacterial sepsis.
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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. bacterial sepsis.