Toll-like receptor 4 plays a crucial role in the immune-adrenal response to endotoxemia

Sepsis and septic shock are leading killers in the non-coronary intensive care unit and still remain worldwide health concerns. The initial host' defense to bacterial infections involves Toll-like receptors (TLRs), which detect and respond to microbial ligands. In addition, a coordinated response of the adrenal and immune system is crucial for survival during severe inflammation. Previously, we have demonstrated a novel 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 mice adrenals. In the present study following LPS-induced stress, 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 cross-talk 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 spepsis.