The vagal innervation of the gut and immune homeostasis

Abstract

The central nervous system interacts dynamically with the immune system to modulate inflammation through humoral and neural pathways. Recently, in animal models of sepsis, the vagus nerve (VN) has been proposed to play a crucial role in the regulation of the immune response, also referred to as the cholinergic anti-inflammatory pathway. The VN, through release of acetylcholine, dampens immune cell activation by interacting with α-7 nicotinic acetylcholine receptors. Recent evidence suggests that the vagal innervation of the gastrointestinal tract also plays a major role controlling intestinal immune activation. Indeed, VN electrical stimulation potently reduces intestinal inflammation restoring intestinal homeostasis, whereas vagotomy has the reverse effect. In this review, we will discuss the current understanding concerning the mechanisms and effects involved in the cholinergic anti-inflammatory pathway in the gastrointestinal tract. Deeper investigation on this counter-regulatory neuroimmune mechanism will provide new insights in the cross-talk between the nervous and immune system leading to the identification of new therapeutic targets to treat intestinal immune disease.

Preliminary report: modulation of parasympathetic nervous system tone influences oesophageal pain hypersensitivity

“…Considering that the parasympathetic nervous system (PNS) is broadly antinociceptive and the sympathetic nervous system (SNS) pro-nociceptive, the implication arises that a balance between them is required for normal pain perception 5. Indeed, accumulating evidence suggests that such an imbalance may represent an important pathophysiological factor in disorders where visceral pain and inflammation are a prominent feature 6. Previously, we have developed and validated a human model of oesophageal pain hypersensitivity where following acid infusion into the distal oesophagus, pain thresholds (PTs) to electrical stimulation in the non-acid exposed proximal oesophagus are reduced due to central sensitisation 7.…”

Lower heart rate variability predicts increased level of C‐reactive protein 4 years later in healthy, nonsmoking adults

“…For example, the inflammatory reflex is a physiological mechanism through which the vagus nerve regulates immune function. Accordingly, efferent vagal activity inhibits the release of pro‐inflammatory cytokines via the release of acetylcholine and this physiological mechanism has been termed the cholinergic anti‐inflammatory pathway . Moreover, the release of IL‐6 and other cytokines triggers the hepatic synthesis of C‐reactive protein (CRP) .…”

The Gut’s Little Brain in Control of Intestinal Immunity

“…Reciprocally, blockade of the cytokines IL-1 β , IL-6, and TNF abolishes this response. These findings were later supported by the observation that vagal ganglia express IL-1 receptors, providing a direct mechanism by which IL-1 β can directly activate vagal nerve afferent fibers [42]. …”

“…Murine peritoneal macrophages express nAChR α 2–7 and 10, nAChR β 2 and 4, and all muscarinic receptors [54], whereas human primary macrophages express nAChR α 2,4, and 7, nAChR β 2 and 4, and mAChR1,4, and 5. Transcripts for nicotinic acetylcholine receptors (nAChRs) subunit α 7, beta2, and alpha4 have been detected in multiple inflammatory cell types, including macrophages derived from various tissues and intestinal lamina propria [43, 55, 56]. The finding of distinct nAChR subtypes expressed in immune cells suggests that nicotine may differentially affect distinct inflammatory cells with its specificity based on receptor affinity for ACh, as is the case in neurons (reviewed in [57]).…”