ACTIVATION OF VAGAL AFFERENTS AFTER INTRAVENOUS-INJECTION OF INTERLEUKIN-1-BETA - ROLE OF ENDOGENOUS PROSTAGLANDINS

Intravenous administration of interleukin-1 (IL-1) activates central a utonomic neuronal circuitries originating in the nucleus of the solita ry tract (NTS). The mechanism(s) by which bloodborne IL-1 regulates br ain functions, whether by operating across the blood-brain barrier and /or by activating peripheral sensory afferents, remains to be characte rized. It has been proposed that vagal afferents originating in the pe riphery may monitor circulating IL-1 levels, because neurons within th e NTS are primary recipients of sensory information from the vagus ner ve and also exhibit exquisite sensitivity to blood-borne IL-1. In this study, we present evidence that viscerosensory afferents of the vagus nerve respond to intravenously administered IL-1 beta. Specific label ing for mRNAs encoding the type 1 IL-1 receptor and the EP3 subtype of the prostaglandin E2 receptor was detected in situ over neuronal cell bodies in the rat nodose ganglion. Moreover, intravenously applied IL -1 increased the number of sensory neurons in the nodose ganglion that express the cellular activation marker c-Fos, which was matched by an increase in discharge activity of vagal afferents arising from gastri c compartments. This response to IL-1 administration was attenuated in animals pretreated with the cyclooxygenase inhibitor indomethacin, su ggesting partial mediation by prostaglandins. In conclusion, these res ults demonstrate that somata and/or fibers of sensory neurons of the v agus nerve express receptors to IL-1 and prostaglandin E2 and that cir culating IL-1 stimulates vagal sensory activity via both prostaglandin -dependent and -independent mechanisms.