RT Journal Article
SR Electronic
T1 Time-of-Day-Dependent Gating of the Liver-Spinal Axis Initiates an Anti-Inflammatory Reflex in the Rat
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0463-20.2020
DO 10.1523/ENEURO.0463-20.2020
VO 7
IS 6
A1 Eva Soto-Tinoco
A1 Esteban Santacruz
A1 María del Carmen Basualdo-Sigales
A1 Natalí N. Guerrero-Vargas
A1 Ruud M. Buijs
YR 2020
UL http://www.eneuro.org/content/7/6/ENEURO.0463-20.2020.abstract
AB The autonomic nervous system (ANS) modulates the immune response through the engagement of an anti-inflammatory reflex. There is controversy regarding which efferent branch of the ANS, sympathetic or parasympathetic, downregulates the intensity of the inflammatory response. Furthermore, how information about the immune status of the body reaches the CNS to engage this reflex remains unclear. The present study demonstrates the existence of a liver-spinal axis that conveys early circulating inflammatory information to the CNS in response to lipopolysaccharide (LPS) and serves as the afferent arm of a sympathetic anti-inflammatory reflex. Furthermore, brainstem and spinal cord visceral sensory neurons show a time-of-day-dependent sensitivity to the incoming inflammatory information, in particular, prostaglandins (PG). Consequentially, the liver-spinal axis promotes the retention of tumor necrosis factor α (TNFα) in the liver and spleen during the resting period, resulting in low plasmatic TNFα levels. Consistently, low sensitivity for LPS during the active period promotes the release of TNFα from the organs into the circulation, resulting in high plasmatic TNFα levels. The present novel findings illustrate how the time-of-day-dependent activation of the liver-spinal axis contributes to the daily fluctuations of the inflammatory response.