4.1 Article

Reflex regulation of systemic inflammation by the autonomic nervous system

Journal

AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL
Volume 237, Issue -, Pages -

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ELSEVIER
DOI: 10.1016/j.autneu.2021.102926

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Funding

  1. National Health and Medical Research Council of Australia [1186382, 1186384]
  2. Victorian Government Operational Infrastructural Support Program

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This review discusses the concept, mechanisms, and role of the inflammatory reflex in regulating inflammation. The reflex exerts its anti-inflammatory effects by suppressing pro-inflammatory cytokines and enhancing anti-inflammatory cytokines, and it is distributed among the abdominal viscera, capable of functioning independently of specific organs.
This short review focusses on the inflammatory reflex, which acts in negative feedback manner to moderate the inflammatory consequences of systemic microbial challenge. The historical development of the inflammatory reflex concept is reviewed, along with evidence that the endogenous reflex response to systemic inflammation is mediated by the splanchnic sympathetic nerves rather than by the vagi. We describe the coordinated nature of this reflex anti-inflammatory action: suppression of pro-inflammatory cytokines coupled with enhanced levels of the anti-inflammatory cytokine, interleukin 10. The limited information on the afferent and central pathways of the reflex is noted. We describe that the efferent anti-inflammatory action of the reflex is distributed among the abdominal viscera: several organs, including the spleen, can be removed without disabling the reflex. Understanding of the effector mechanism is incomplete, but it probably involves a very local action of neurally released noradrenaline on beta(2) adrenoceptors on the surface of tissue resident macrophages and other innate immune cells. Finally we speculate on the biological and clinical significance of the reflex, citing evidence of its power to influence the resolution of experimental bacteraemia.

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