TY - JOUR
T1 - Neural reflex regulation of systemic inflammation
T2 - Potential new targets for sepsis therapy
AU - Fernandez, Ricardo
AU - Nardocci, Gino
AU - Navarro, Cristina
AU - Reyes, Edison P.
AU - Acuña-Castillo, Claudio
AU - Cortes, Paula P.
N1 - Publisher Copyright:
© 2014 Fernandez, Nardocci, Navarro, Reyes, Acuña-Castillo and Cortes.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Carotid body
KW - Reflex control of inflammation
KW - Sepsis
KW - Systemic inflammation
KW - Vagus nerve
UR - http://www.scopus.com/inward/record.url?scp=84922019089&partnerID=8YFLogxK
U2 - 10.3389/fphys.2014.00489
DO - 10.3389/fphys.2014.00489
M3 - Review article
AN - SCOPUS:84922019089
SN - 1664-042X
VL - 5
JO - Frontiers in Physiology
JF - Frontiers in Physiology
IS - DEC
M1 - 489
ER -