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Neural and endocrine function in the immune response to critical illness 

Neural and endocrine function in the immune response to critical illness
Neural and endocrine function in the immune response to critical illness

Gareth L. Ackland

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date: 17 May 2022

The neurohormonal physiological response to various stressors is pivotal for maintaining homeostasis. However, the advent of modern critical care has distorted evolutionary biology by generating the entirely new (patho)physiological entity of critical illness. By extending the biological features of the ‘fight or flight’ response beyond the acute phase, distinct neurohormonal, and immune profiles have become increasingly apparent. Both direct and off-target effects of neurohormonal control on immune function are implicated in the disruption of bidirectional links between neurohormones and immune effectors that limit organ dysfunction. Iatrogenic factors introduced by critical care therapy may exacerbate neurohormonal dysregulation, further distorting the biology of the ‘fight or flight’ response. Neural mechanisms underlying this newly-characterized clinical syndrome remain poorly understood. Furthermore, the same neurohormonal responses are chronically dysregulated in pre-existing comorbidities diseases associated with an increased risk of sepsis, multi-organ failure and critical illness. Off-target local immune effects may explain the failure of clinical trials aimed at altering systemic neurohormonal physiology. Recent laboratory and translational human clinical studies, particularly in diseases characterized by chronic neurohormonal dysregulation, have provided new insights into the possibility of therapeutic interventions that could minimize the pathophysiological features of critical illness.

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