Exp Clin Endocrinol Diabetes 2015; 123 - P09_06
DOI: 10.1055/s-0035-1547699

The role of hematopoietic TLR-signaling in sepsis-associated adrenal inflammation and the HPA axis activation

W Kanczkowski 1, A Neuwirth 2, S Grossklaus 2, K Zacharowski 3, T Chavakis 2, SR Bornstein 4
  • 1Department of Medicine III, Faculty of Medicine of the Technische Universität Dresden
  • 2Department of Clinical Pathobiochemistry, Faculty of Medicine, Technische Universität Dresden
  • 3University Hospital Frankfurt; Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy
  • 4Technische Universität Dresden; Universitätsklinikum Carl Gustav Carus Dresden; Medizinische Klinik und Poliklinik III

Sepsis and septic shock in response to bacterial or viral infections are leading cause of death among critically ill patients. Activation of the hypothalamic-pituitary-adrenal (HPA) axis stress system is pivotal to cope with and to survive these adverse conditions. However, in many critically ill patients, the production of adrenal glucocorticoids, their peripheral action and metabolism are often impaired.

Previously, we have demonstrated that an intact TLR-signaling in myeloid and liver cells but not in adrenocortical cells controls the adrenal activation and inflammation during endotoxemia. In the present study, we have asked whether these effects were solely attributed to the immune system or also to other organs including the liver. Therefore, we have generated mice with the hematopoietic-specific deletion of a TLR-major adapter molecule – Myeloid differentiation primary response gene 88 (MyD88).

By engaging Vav-Cre-MyD88 fl/fl mice to LPS, we demonstrated that an intact TLR-signaling in the hematopoietic cells only is the major regulator of adrenal gland inflammation, including enhanced expression of pro-inflammatory mediators and immune cell infiltration. In addition, we identified that an intact TLR signaling in immune cells was necessary for a proper activation of the HPA axis.

Thus, our data suggest that an intact TLR signaling in immune cells rather than in other cells is critically involved in the regulation of the immune-adrenal crosstalk regulating the adrenal glucocorticoid production and inflammation.