Cytokine-induced alterations of gastrointestinal motility in gastrointestinal disorders

Abstract

Inflammation and immune activation in the gut are usually accompanied by alteration of gastrointestinal (GI) motility. In infection, changes in motor function have been linked to host defense by enhancing the expulsion of the infectious agents. In this review, we describe the evidence for inflammation and immune activation in GI infection, inflammatory bowel disease, ileus, achalasia, eosinophilic esophagitis, microscopic colitis, celiac disease, pseudo-obstruction and functional GI disorders. We also describe the possible mechanisms by which inflammation and immune activation in the gut affect GI motility. GI motility disorder is a broad spectrum disturbance of GI physiology. Although several systems including central nerves, enteric nerves, interstitial cells of Cajal and smooth muscles contribute to a coordinated regulation of GI motility, smooth muscle probably plays the most important role. Thus, we focus on the relationship between activation of cytokines induced by adaptive immune response and alteration of GI smooth muscle contractility. Accumulated evidence has shown that Th1 and Th2 cytokines cause hypocontractility and hypercontractility of inflamed intestinal smooth muscle. Th1 cytokines downregulate CPI-17 and L-type Ca(2+) channels and upregulate regulators of G protein signaling 4, which contributes to hypocontractility of inflamed intestinal smooth muscle. Conversely, Th2 cytokines cause hypercontractilty via signal transducer and activator of transcription 6 or mitogen-activated protein kinase signaling pathways. Th1 and Th2 cytokines have opposing effects on intestinal smooth muscle contraction via 5-hydroxytryptamine signaling. Understanding the immunological basis of altered GI motor function could lead to new therapeutic strategies for GI functional and inflammatory disorders.

Mucosally Expressed Cytokines are Associated with the Esophageal Motility Function

“…The strong network among the enteric nerves, interstitial cells of Cajal, and smooth muscles plays a pivotal role in the regulation of GI motility. Inflammation, which is affected by cytokines, alters the GI motility function [8]. Evidence of cytokine-induced alteration of the GI motility has been provided by several basic studies [11-13, 15, 16, 20].…”

“…On the other hand, it has been reported that each Th cell subset is linked to gastrointestinal (GI) smooth muscle contractility [8]. The accumulated evidence has shown that Th1- and Th2-related cytokines contribute to decreased or increased GI contractility respectively.…”

Colitis-induced neuroplasticity disrupts motility in the inflamed and post-inflamed colon

“…These include changes within the colon such as the loss of neurons (20,21), muscle changes such as hypertrophy, altered ionic conductances and responsiveness to neurotransmitters (45,46), changes in mucosal serotonin signaling that appear to result in increased serotonin availability in inflamed regions (47), and changes in the physical compliance of the bowel in inflamed regions due to fibrosis. Changes in the sensitivity of extrinsic afferent neurons and/ or changes in sympathetic input could also contribute to altered colon function as well (33).…”

Effects of Exogenous Interleukin-9 on the Growth, Proliferation and Activity of Interstitial Cells of Cajal Cultured in vitro

“…Recently, it was found that the damage, loss or function change of ICCs is closely associated with many GI motility disorders after inflammation [5][6][7] . Hence, further studies about the growth, development and maintaining mechanism of the network structure of ICCs in pathologic condition and the cytokines, which regulate the maintenance and survival of ICCs are of great clinical significance [8].…”