Interleukin1b in Immune Cells of the Abdominal Vagus Nerve: a Link between the Immune and Nervous Systems (original) (raw)
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The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
Intraperitoneal administration of the cytokine interleukin-1 (IL-1) induces brain-mediated sickness symptoms that can be blocked by subdiaphragmatic vagotomy. Intraperitoneal IL-1 also induces expression of the activation marker c-fos in vagal primary afferent neurons, suggesting that IL-1 is a key component of vagally mediated immune-to-brain communication.
Interleukin1 induces c-Fos immunoreactivity in primary afferent neurons of the vagus nerve
Brain Research, 1998
Peripheral administration of bacterial endotoxin, an immune stimulant, induces evidence of activation in vagal primary afferent neurons. To determine whether interleukin-1β (IL-1β) is part of the molecular pathway leading to this activation, we assessed the expression of the neuronal activation marker c-Fos in vagal primary afferent neurons after intraperitoneal injections of IL-1β (2 μg/kg). IL-1β, but not vehicle, induced c-Fos
Cytokine-specific Neurograms in the Sensory Vagus Nerve
Bioelectronic Medicine
The vagus nerve is primarily sensory, and it is the principal conduit that relays afferent signals from the visceral organs to the brainstem. Seminal studies by Linda Watkins revealed that an intact vagus nerve is required for the development of pyrexia in response to intra-abdominal IL-1β administration (4,5). Moreover, early work by Niijima (6-8) suggested that IL-1β might activate signaling in peripheral vagus afferents. Sensory neurons express cytokine receptors, including TNF and IL-1β receptors, and change their activation thresholds when exposed to the corresponding cytokines (9-11). This work, together with other studies, suggests that the vagus nerve may be an important component of a peripheral neural network capable of reporting changes in peripheral inflammation and immunity. Here we reasoned that the vagus nerve transmits specific neural signatures in response to specific cytokines. immune responses. A prototypical neural pathway is the inflammatory reflex (1), defined by the electrical signals transmitted in the vagus nerve to the splenic nerve, culminating in a specialized subset of T lymphocytes that release acetylcholine (2,3). This T cell-derived neurotransmitter signals via a mechanism that depends on α-7 nicotinic acetylcholine receptors (α-7nAChR) to inhibit cytokine production by splenic macrophages (2).
Effects of vagotomy on lipopolysaccharide-induced brain interleukin-1β protein in rats
Autonomic Neuroscience-basic & Clinical, 2000
The production of interleukin-1b (IL-1b) in brain is thought to be a critical step in the induction of central manifestations of the acute phase response, and the vagus nerve has been implicated in immune-to-brain communication. Thus, this study examined the effects of intraperitoneal (i.p.) injections of lipopolysaccharide (LPS) on brain IL-1b protein levels in control and subdiaphragmatically vagotomized rats. In the first experiment, vagotomized and sham-operated male Sprague-Dawley rats were injected i.p. with one of three doses (10, 50, 100 mg / kg) of LPS or vehicle (sterile, pyrogen-free saline) and sacrificed 2 h after the injection. In the second experiment, vagotomized and sham-operated rats were injected i.p. with 100 mg / kg LPS or vehicle and sacrificed 1 h after the injection. The i.p. injection of LPS dose-dependently increased IL-1b protein levels in the hypothalamus, hippocampus, dorsal vagal complex, cerebellum, posterior cortex, and pituitary 2 h after the injection. Brain and pituitary IL-1b levels were also significantly increased 1 h after the injection of 100 mg / kg LPS. There were no significant differences in brain IL-1b levels between sham-operated and vagotomized rats at either the 2 h or 1 h time points. The current data are consistent with previous studies showing increases in brain IL-1b after peripheral injections of LPS, and support the notion that brain IL-1b is a mediator in the illness-induction pathway. Furthermore, these data indicate that, at the doses and times tested, subdiaphragmatic vagal afferents are not crucial for LPS-induced brain IL-1b protein.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
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 bloodborne 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-1. 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 prostaglandindependent and -independent mechanisms.
Brain, Behavior, and Immunity, 2005
Peripheral injection of bacterial endotoxin lipopolysaccharide (LPS) activates the paraventricular nuclei of the hypothalamus (PVN), and consequently the hypothalamuspituitary adrenal axis. Inflammatory cytokine interleukin-1 (IL-1) has been considered as a key mediator that translates the peripheral LPS stimulation into neuronal activation in the PVN. Several studies attempting to localize the expression of receptors for IL-1 (IL-1R), however, have failed to detect IL-1R on PVN neurons. It remains unclear, therefore, how IL-1 might stimulate the neurons of the PVN. In this study, we traced the cellular responsiveness to IL-1 by measuring the mRNA production of the cytokine responsive gene IκBα in the PVN. After either peripheral injection LPS or intracerebroventricular (i.c.v.) injection of IL-1β, IκBα mRNA was found mostly in endothelial cells of the brain with the highest level of expression in PVN blood vessels. In addition, both injections also induced the expression of cyclooxygenase-2 in brain endothelial cells. Pretreatment with indomethacin, a cyclooxygenase inhibitor, blocked LPS and IL-1 induced neuronal activation in the PVN, but did not reduce the induction of IκBα in PVN endothelium. These results show that IL-1 acting on the endothelial cells of the brain, particularly in the PVN, may be an intermediate step relating peripheral immune signals to the brain.
Interleukin-1 alpha and vasoactive interstinal peptide: Enigmatic regulation of neuronal survival
1995
Abstraet--A neurotrophic role for interleukin-1 alpha (IL-la) was investigated in dissociated spinal cord-dorsal root ganglion cultures. Three observations suggested a survival-promoting action for IL-lc~ in nine-day-old cultures: (1) neutralizing antiserum to murine 1L-lc~ decreased neuronal survival; (2) treatment with IL-la in electrically blocked cultures increased neuronal survival; and (3) antiserum to the type I IL-1 receptor decreased neuronal survival. Treatment with VIP prevented neuronal cell death associated with the antiserum to IL-la. In contrast, treatment of one-month-old cultures with IL-lc~ produced neuronal cell death and neutralizing antiserum to the IL-1 receptor had no effect on neuronal survival in these cultures. These experiments suggested that an IL-l-like substance was necessary for neuronal survival during a specific stage in development and that a relationship between VIP and IL-lc~ might account in part for the neurotrophic properties of VIP.
Vagal immune-to-brain communication: a visceral chemosensory pathway
Autonomic Neuroscience, 2000
The immune system operates as a diffuse sensory system, detecting the presence of specific chemical constituents associated with dangerous micro-organisms, and then signalling the brain. In this way, immunosensation constitutes a chemosensory system. Several submodalities of this sensory system function as pathways conveying immune-related information, and can be classified as either primarily brain barrier associated or neural. The vagus nerve provides the major neural pathway identified to date. The initial chemosensory transduction events occur in immune cells, which respond to specific chemical components expressed by dangerous micro-organisms. These immune chemosensory cells release mediators, such as cytokines, to activate neural elements, including primary afferent neurons of the vagal sensory ganglia. Primary afferent activation initiates local reflexes (e.g. cardiovascular and gastrointestinal) that support host defense. In addition, at least three parallel pathways of ascending immune-related information activate specific components of the illness response. In this way, immunosensory systems represent highly organized and coherent pathways for activating host defense against infection.