The role of hormones in sepsis: an integrated overview with a focus on mitochondrial and immune cell dysfunction

Abstract

Sepsis is a dysregulated host response to infection that results in life-threatening organ dysfunction. Virtually every body system can be affected by this syndrome to greater or lesser extents. Gene transcription and downstream pathways are either up- or downregulated, albeit with considerable fluctuation over the course of the patient's illness. This multi-system complexity contributes to a pathophysiology that remains to be fully elucidated. Consequentially, little progress has been made to date in developing new outcome-improving therapeutics. Endocrine alterations are well characterised in sepsis with variations in circulating blood levels and/or receptor resistance. However, little attention has been paid to an integrated view of how these hormonal changes impact upon the development of organ dysfunction and recovery. Here, we present a narrative review describing the impact of the altered endocrine system on mitochondrial dysfunction and immune suppression, two interlinked and key aspects of sepsis pathophysiology.

Keywords: hormones; immune response; mitochondria; organ dysfunction; sepsis; stress response.

Figure 1. Appropriate (A) and inappropriate (B) host responses to an infectious insult resulting in either resolution of the infection or progression to multiple organ dysfunction

Similar pathways are involved yet, for reasons still unclear, are dysregulated and exaggerated in the latter situation.

Figure 2. Modification of hormonal responses in early (A) and established (B) sepsis with downstream impact on immunity, metabolism, and organ functionality

IGF-1 insulin growth factor-1; ATP adenosine triphosphate.