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Front Physiol. 2014 Dec 15;5:489. doi: 10.3389/fphys.2014.00489. eCollection 2014.

Neural reflex regulation of systemic inflammation: potential new targets for sepsis therapy.

Author information

1
Laboratorio de Fisiología, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas y Facultad de Medicina, Universidad Andrés Bello Santiago, Chile.
2
Centro de Fisiología Celular e Integrativa, Facultad de Medicina, Clínica Alemana - Universidad del Desarrollo Santiago, Chile ; Dirección de Investigación, Universidad Autónoma de Chile Santiago, Chile.
3
Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile Santiago, Chile.
4
Laboratorio de Fisiología, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas y Facultad de Medicina, Universidad Andrés Bello Santiago, Chile ; BioAdvising Santiago, Chile.

Abstract

Sepsis progresses to multiple organ dysfunction due to the uncontrolled release of inflammatory mediators, and a growing body of evidence shows that neural signals play a significant role in modulating the immune response. Thus, similar toall other physiological systems, the immune system is both connected to and regulated by the central nervous system. The efferent arc consists of the activation of the hypothalamic-pituitary-adrenal axis, sympathetic activation, the cholinergic anti-inflammatory reflex, and the local release of physiological neuromodulators. Immunosensory activity is centered on the production of pro-inflammatory cytokines, signals that are conveyed to the brain through different pathways. The activation of peripheral sensory nerves, i.e., vagal paraganglia by the vagus nerve, and carotid body (CB) chemoreceptors by the carotid/sinus nerve are broadly discussed here. Despite cytokine receptor expression in vagal afferent fibers, pro-inflammatory cytokines have no significant effect on vagus nerve activity. Thus, the CB may be the source of immunosensory inputs and incoming neural signals and, in fact, sense inflammatory mediators, playing a protective role during sepsis. Considering that CB stimulation increases sympathetic activity and adrenal glucocorticoids release, the electrical stimulation of arterial chemoreceptors may be suitable therapeutic approach for regulating systemic inflammation.

KEYWORDS:

carotid body; reflex control of inflammation; sepsis; systemic inflammation; vagus nerve

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