Neuro-immune interaction in inflammatory bowel disease and irritable bowel syndrome: Future therapeutic targets

Division Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Sciences, Utrecht University, PO box 80082, 3508 TB Utrecht, The Netherlands.
European Journal of Pharmacology (Impact Factor: 2.53). 06/2008; 585(2-3):361-74. DOI: 10.1016/j.ejphar.2008.02.095
Source: PubMed


The gastro-intestinal tract is well known for its largest neural network outside the central nervous system and for the most extensive immune system in the body. Research in neurogastroenterology implicates the involvement of both enteric nervous system and immune system in symptoms of inflammatory bowel disease and irritable bowel syndrome. Since both disorders are associated with increased immune cell numbers, nerve growth and activation of both immune cells and nerves, we focus in this review on the involvement of immune cell-nerve interactions in inflammatory bowel disease and irritable bowel syndrome. Firstly, the possible effects of enteric nerves, especially of the nonadrenergic and noncholinergic nerves, on the intestinal immune system and their possible role in the pathogenesis of chronic intestinal inflammatory diseases are described. Secondly, the possible effects of immunological factors, from the innate (chemokines and Toll-like receptors) as well as the adaptive (cytokines and immunoglobulins) immune system, on gastro-intestinal nerves and its potential role in the development of inflammatory bowel disease and irritable bowel syndrome are reviewed. Investigations of receptor-mediated and intracellular signal pathways in neuro-immune interactions might help to develop more effective therapeutic approaches for chronic inflammatory intestinal diseases.

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    • "Autonomic dysregulation has been described in IBD and IBS [Ananthakrishnan et al. 2010; Tougas, 2000]. This dysregulation may be due to chronic inflammation through nitric oxide induced nerve damage [Kraneveld et al. 2008]. Furthermore, as research has indicated that patients with IBS may have alterations in brain regulatory centers (e.g. the anterior cingulate cortex) [Tillisch et al. 2011], there also may be CNS changes in patients with IBD and persistent pain. "
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    ABSTRACT: Abdominal pain is a common symptom in patients with inflammatory bowel disease (IBD) and has a profound negative impact on patients' lives. There are growing data suggesting that pain is variably related to the degree of active inflammation. Given the multifactorial etiologies underlying the pain, the treatment of abdominal pain in the IBD population is best accomplished by individualized plans. This review covers four clinically relevant categories of abdominal pain in patients with IBD, namely, inflammation, surgical complications, bacterial overgrowth, and neurobiological processes and how pain management can be addressed in each of these cases. The role of genetic factors, psychological factors, and psychosocial stress in pain perception and treatment will also be addressed. Lastly, psychosocial, pharmacological, and procedural pain management techniques will be discussed. An extensive review of the existing literature reveals a paucity of data regarding pain management specific to IBD. In addition, there is growing consensus suggesting a spectrum between IBD and irritable bowel syndrome (IBS) symptoms. Thus, this review for adult and pediatric clinicians also incorporates the literature for the treatment of functional abdominal pain and the clinical consensus from IBD and IBS experts on pharmacological, behavioral, and procedural methods to treat abdominal pain in this population.
    Therapeutic Advances in Gastroenterology 09/2012; 5(5):339-57. DOI:10.1177/1756283X12446158 · 3.93 Impact Factor
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    • "The current concepts on neuroimmune interactions in the gut are almost exclusively based on data from cellular or organ responses in animal models. A number of recent reviews elegantly summarized such findings and the interested reader is referred to them [1] [2] [3] [4] [5]. We like to review primarily the evidence for the functional mast cell–nerve axis in the human gut. "
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    ABSTRACT: This paper summarizes the current knowledge on the interactions between intestinal mast cells, enteric neurons and visceral afferents which are part of the gut brain axis. The focus of this review is on the relevance of the mast cell-nerve axis in the human intestine. Similarities and important differences in the organization of the mast cell-nerve axis between human and rodents are discussed. Functionally important human mast cell mediators with neural actions in the human ENS are histamine (H1-4 receptors), proteases (PAR1 receptors), several cytokines and chemokines and probably also serotonin (5-HT(3) receptors). On the other hand, mediator release from human intestinal mast cells is modulated by neuropeptides released from enteric and visceral afferent nerves. This article is part of a Special Issue entitled: Mast Cells in Inflammation.
    Biochimica et Biophysica Acta 06/2011; 1822(1):85-92. DOI:10.1016/j.bbadis.2011.06.004 · 4.66 Impact Factor
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    • "The results showed that the abnormal number of EC cells and 5-HT level were correlated with the increased c-fos in CNS, which supported the hypothesis that the activation of CNS may induce activation of EC cells in the colon and then the release of 5-HT. There is ample evidence for elevated level of 5-HT in the colon of IBS patients [28–31]. EC cells are likely sources. "
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    ABSTRACT: Although visceral hypersensitivity is a major pathophysiological feature of irritable bowel syndrome (IBS), its molecular mechanisms are still poorly understood. c-fos is a well-established marker of cell activation. Accumulating evidence demonstrates that norepinephrine (NE) system is dysregulated in IBS; however, very little is known on its mechanism. It is our hypothesis that elevated expression of c-fos in central nervous system (CNS) correlates with visceral hypersensitivity in rat model of IBS. Furthermore, we explored the changes of NE system in IBS patients. The rat model of IBS was induced by heterotypic chronic and acute stress. Tissues obtained from rat model were analyzed for c-fos levels in CNS (frontal lobe, hippocampus, cornu dorsale) and colon by immunohistochemistry. Real-time reverse transcription polymerase chain reaction was used to detect tyrosine hydroxylase (TH) in the colonic tissues obtained from IBS patients. The rat model of IBS was associated with increased expression of c-fos in different parts of CNS (P = 0.001, P = 0.002, and P = 0.002, respectively), but normal in colon (P = 0.207). The clinical parameters (colonic motility and sensation) of rat model were significantly correlated with elevated c-fos in CNS (P < 0.05). Enterochromaffin cells and serotonin in colon were related to the elevated c-fos in CNS (P < 0.05). The TH messenger ribonucleic acid (mRNA level of IBS-D patients was almost four times as much as that of controls. Elevated expression of c-fos in CNS might be one of key mechanisms in etiology of IBS. Therefore, regulation of CNS activation could be a major targeting effect when treating IBS patients.
    International Journal of Colorectal Disease 02/2011; 26(8):1035-44. DOI:10.1007/s00384-011-1153-4 · 2.45 Impact Factor
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