Review
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World J Gastrointest Pathophysiol. Oct 15, 2011; 2(5): 72-81
Published online Oct 15, 2011. doi: 10.4291/wjgp.v2.i5.72
Cytokine-induced alterations of gastrointestinal motility in gastrointestinal disorders
Hirotada Akiho, Eikichi Ihara, Yasuaki Motomura, Kazuhiko Nakamura
Hirotada Akiho, Eikichi Ihara, Yasuaki Motomura, Kazuhiko Nakamura, Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Author contributions: All authors contributed extensively in preparing this manuscript; Akiho H provided a significant editorial and literature contribution; Nakamura K and Motomura Y performed the literature review; Ihara E provided literature related comments and review.
Correspondence to: Hirotada Akiho, MD, PhD, Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. akiho@intmed3.med.kyushu-u.ac.jp
Telephone: +81-92-6425286 Fax: +81-92-6425287
Received: March 31, 2011
Revised: August 12, 2011
Accepted: August 19, 2011
Published online: October 15, 2011
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 Ca2+ 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.

Keywords: Cytokine; Motility; Inflammation; Immunology