Airway Chemosensitive Receptors in Vagus Nerve Perform Neuro-Immune Interaction for Lung-Brain Communication

Abstract

Recently, IL-1β has been found to activate airway C-fiber receptors (CFRs) and high threshold Aδ 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-1β 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-α (1 μg/ml, 20 μl) 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-α was significantly attenuated by mixing with neutralizing antibody (10 μg/ml, 20 μl). The activities were 0.31±0.09 and 0.57±0.16 imp/s for control and injection of the TNF-α mixture (n=9; P<0.01), respectively. These nociceptors did not respond to location injection of normal saline. Our results show that TNF-α, like IL-1β, can activate airway nociceptors. It lends support to the hypothesis that airway nociceptors in the lung mediate the innate immune response.