Article

The Cholinergic Anti-inflammatory Pathway: A Missing Link in Neuroimmunomodulation

Laboratory of Biomedical Science, North Shore LIJ-Research Institute, Manhasset, NY 11030, USA.
Molecular Medicine (Impact Factor: 4.51). 05/2003; 9(5-8):125-34.
Source: PubMed

ABSTRACT

This review outlines the mechanisms underlying the interaction between the nervous and immune systems of the host in response to an immune challenge. The main focus is the cholinergic anti-inflammatory pathway, which we recently described as a novel function of the efferent vagus nerve. This pathway plays a critical role in controlling the inflammatory response through interaction with peripheral a7 subunit-containing nicotinic acetylcholine receptors expressed on macrophages. We describe the modulation of systemic and local inflammation by the cholinergic anti-inflammatory pathway and its function as an interface between the brain and the immune system. The clinical implications of this novel mechanism also are discussed.

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    • "The activation of these receptors decreases the release of proinflammatory mediators (Gallowitsch-Puerta and Tracey, 2005;Johnston and Webster 2009;Pavlov et al., 2003;Otmishi et al., 2008;Wang et al., 2003). Suppression of pro-inflammatory cytokine release by increased vagal efferent activity has been shown to protect against conditions associated with systemic or pulmonary inflammatory responses (Bencherif et al., 2011;Borovikova et al., 2000;Guarini et al., 2003;Pavlov et al., 2003;van Westerloo et al., 2006). ARDS being an acute inflammatory disorder, it is likely that such vagally mediated mechanisms are involved in the pathophysiology. "
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    ABSTRACT: Mesobuthus tamulus (MBT) venom and oleic acid (OA) have been shown to produce acute respiratory distress syndrome (ARDS) involving different mechanisms. The role of vagally mediated anti-inflammatory pathway in ARDS is poorly understood. Therefore, the effects of vagal efferent stimulation on these two models of ARDS were examined. Experiments were performed on anesthetized adult rats. Parameters like ventilatory changes (respiratory frequency and minute ventilation), hypoxemic status (PaO2/FiO2 ratio; P/F ratio), survival time, pulmonary water content and histopathological evidences of lung injury were determined to assess the severity of ARDS. In addition, heart rate (HR) and mean arterial pressure (MAP) were monitored. Injection of OA/MBT venom produced respiratory alterations, hypoxemia, pulmonary edema and histopathological changes demonstrating the development of ARDS. In both the groups, animals died around 60 min. Tachypnea and hyperventilation were seen after OA while bradypnea and hypoventilation were seen after MBT venom. Pulmonary edema was absent in vagotomised animals in MBT venom group but not in OA group. Further, electrical stimulation of the cut peripheral ends of vagii prolonged the survival time and attenuated all the parameters of MBT venom-induced ARDS significantly. In case of OA, there was improvement in histopathological changes but the survival time of animals was not prolonged. Stimulation of α7-nicotinic receptors (by pretreatment with GTS-21) exacerbated OA as well as MBT venom-induced ARDS. The present results indicate that vagal efferent stimulation protects against MBT venom-induced ARDS.
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    • "Based on adult literature, nonpharmacologic strategies have been designed for use in the pediatric patient, but there remains a lack of evidence for pharmacologic treatment when these measures fail (Meagher 2001). Multiple central nervous system pathways have been implicated in the development of delirium , including dopaminergic, serotoninergic, glutaminergic, and cholinergic pathways in the cerebral cortex, striatum, substantia nigra, and thalamus (Pavlov et al. 2003; Gunther et al. 2008). This makes pharmacotherapy with psychoactive agents, particularly quetiapine, a physiologically reasonable choice. "
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    • "The afferent and efferent limbs of the vagus nerve constitute the cholinergic antiinflammatory pathway (Pavlov et al., 2003; Tracey, 2002) which acts as an interface "
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