Benutzerspezifische Werkzeuge

Objectives/Aims

Adrenal gland dysregulation is a common event during sepsis. Unfortunately, the responsible mechanisms are not fully understood. Our results obtained during the previous funding period strongly suggest that a rapid cell death and local adrenal inflammation, which occurs in the adrenal gland during both LPS- induced SIRS and polymicrobial sepsis may play a crucial role in this process. This hypothesis will be addressed through the following objectives.

(I) First, we will characterize the role of intact adrenocortical and hematopoietic TLR-signaling in the sepsis mediated adrenal gland inflammation, cell death and steroidogenesis in a long term sepsis model (polymicrobial sepsis).

(II) Second, we will study the mechanisms involved in a sepsis-mediated inflammation and cell death of adrenal cells. We will focus on the potential involvement of infiltrating immune cells and mitochondrial function and dysfunction in these processes.

(III) In the last aim, we will test whether applications of therapeutic interventions, such as mitochondria-protective agents, dual-blockade of the C5a receptors and anti-inflammatory substances could reverse sepsis-mediated adrenal gland apoptosis and inflammation.