Activation of vagal afferents after intravenous injection of interleukin-1beta: role of endogenous prostaglandins.
Intravenous administration of interleukin-1 (IL-1) activates central autonomic neuronal circuitries originating in the nucleus of the solitary tract (NTS). The mechanism(s) by which blood-borne IL-1 regulates brain functions, whether by operating across the blood-brain barrier and/or by activating peripheral sensory afferents, remains to be characterized. It has been proposed that vagal afferents originating in the periphery may monitor circulating IL-1 levels, because neurons within the NTS are primary recipients of sensory information from the vagus nerve 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-1beta. Specific labeling 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 gastric compartments. This response to IL-1 administration was attenuated in animals pretreated with the cyclooxygenase inhibitor indomethacin, suggesting partial mediation by prostaglandins. In conclusion, these results demonstrate that somata and/or fibers of sensory neurons of the vagus nerve express receptors to IL-1 and prostaglandin E2 and that circulating IL-1 stimulates vagal sensory activity via both prostaglandin-dependent and -independent mechanisms.
Ek
M
M
Department of Medicine, Unit of Rheumatology, The Karolinska Institute, Stockholm, Sweden.
Kurosawa
M
M
Lundeberg
T
T
Ericsson
A
A
D000210:Acute-Phase Reaction / Q000276:immunology; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology; D015232:Dinoprostone / Q000378:metabolism; D007275:Injections, Intravenous; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D015213:Neuroimmunomodulation / Q000502:physiology; D009475:Neurons, Afferent / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology; D009620:Nodose Ganglion / Q000166:cytology / Q000378:metabolism; D011453:Prostaglandins / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D017552:Solitary Nucleus / Q000166:cytology / Q000378:metabolism; D013270:Stomach / Q000294:innervation; D014630:Vagus Nerve / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D007375:Interleukin-1; D011453:Prostaglandins; D016760:Proto-Oncogene Proteins c-fos; D017472:Receptors, Interleukin-1; D015232:Dinoprostone