The present studies evaluate whether the vagus nerves link the lungs' immune and neural systems by transmitting information through pulmonary nociceptors. Single unit activities from pulmonary nociceptors [C fiber receptors (CFRs) and high threshold Adelta fiber receptors (HTARs)] were recorded from the cervical vagus nerve in anesthetized, open-chest, and mechanically ventilated rabbits. Interleukin1beta was then injected into the nociceptor field (IL-1beta, 10 microg/ml, 20 microl). Both CFRs and HTARs were stimulated by the local injection; their activities increased from 0.2+/-0.1 to 1.8+/-0.5 imp/s (n=10; p<0.01), and from 0.2+/-0.1 to 1.1+/-0.1 imp/s, respectively (n=6; p<0.01). These increases were greatly attenuated by simultaneous administration of IL-1beta with IL-1 ra, a natural IL-1 receptor antagonist. The nociceptors were not stimulated by local injection of normal saline. Our data demonstrate that nociceptors can be activated by pro-inflammatory cytokines and support the hypothesis that airway nociceptors transmit immune signals from the lung to the brain.