Airway chemosensitive receptors in vagus nerve perform neuro-immune interaction for lung-brain communication.

Recently, IL-1beta has been found to activate airway C-fiber receptors (CFRs) and high threshold Adelta receptors (HTARs), which may influence innate immune response via activation of the central nervous system. The present study aims to determine whether such a stimulatory effect is restricted to IL-1beta or applies to other pro-inflammatory cytokines. In anesthetized, open-chest, and mechanically ventilated rabbits, we recorded single unit activity from vagal nociceptors and examined their response to microinjection of TNF-alpha (1 microg/ml, 20 microl) directly into the receptive fields. Both CFRs and HTARs had similar responses. Their activity increased from 0.12+/-0.05 to 0.93+/-0.16 imp/s (n=15; P<0.001). This stimulatory effect of TNF-alpha was significantly attenuated by mixing with neutralizing antibody (10 microg/ml, 20 microl). The activities were 0.31+/-0.09 and 0.57+/-0.16 imp/s for control and injection of the TNF-alpha mixture (n=9; P<0.01), respectively. These nociceptors did not respond to location injection of normal saline. Our results show that TNF-alpha, like IL-1beta, can activate airway nociceptors. It lends support to the hypothesis that airway nociceptors in the lung mediate the innate immune response.