Clinical Therapeutics/Volume ], Number ], 2017 Interleukin-10: A Compelling Therapeutic Target in Patients With Irritable Bowel Syndrome Sunil Kumar, PhD 1 ; Ratnakar Shukla, PhD 2 ; Prabhat Ranjan, PhD 2 ; and Awanish Kumar, PhD 3 1 Faculty of Biotechnology, Institute of Bioscience and Technology, Shri Ramswaroop Memorial University, Barabanki, India; 2 Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India; and 3 Department of Biotechnology, National Institute of Technology, Raipur, India ABSTRACT Purpose: Pro- and antiinflammatory cytokines are important modulators of the immune response and play a major role in conditions of intestinal inflammation, such as irritable bowel syndrome (IBS). Cytokine production is regulated genetically, and imbalances in cytokine secre- tion may affect disease susceptibility and clinical out- comes of various conditions. There is a rapidly growing body of evidence to support an etiologic role for gastro- intestinal infection and the associated immune activation in the development of postinfectious IBS. Other factors such as psychological stress, anxiety, and depression may likely be involved in the altered profiles of pro- and antiinflammatory cytokines that lead to chronic IBS. Methods: We searched the literature using PubMed, MEDLINE, and Google Scholar with related key terms and prepared this review article on that basis. Findings: Interleukin (IL)-10 is a regulatory cyto- kine that inhibits both antigen presentation and the release of proinflammatory cytokines. Therefore, it is proposed as a potent antiinflammatory biological therapy for IBS. Implications: Recently, a strong interest in the ther- apeutic potential of IL-10 for IBS has developed. The diverse roles of IL-10 in IBS are reviewed here. We conducted an in-depth review on IL-10 and IBS to address this question. Future studies of IL-10 may provide new insights into IBS therapy. (Clin Ther. 2017; ] :]]] –]]] ) & 2017 Elsevier HS Journals, Inc. All rights reserved. Key words: cytokines, IL-10, inflammation, inflam- matory bowel disease, therapy. INTRODUCTION Irritable bowel syndrome (IBS) is a heterogeneous group of disorders characterized by key symptoms of recurrent abdominal pain or discomfort, abdominal bloating, and altered bowel habits in the absence of an organic cause. 1 The prevalence of IBS varies from 4% to 20% worldwide, and IBS can have a significant negative impact on lifestyle and social well-being. 2,3 Despite the high prevalence of IBS, its etiology and pathophysiology remain enigmatic. However, several hypotheses have been proposed, including altered normal gut flora (dysbiosis), altered brain–gut inter- actions, visceral hypersensitivity, and altered immune activation. 4 Due to the lack of a unifying marker, Rome III criteria are used for the diagnosis of IBS as well as for classifying IBS based on clinical symptoms (ie, IBS with constipation, IBS with diarrhea [IBS-D], mixed/alternating, or unclassified). 5 Evidence from current studies has shown that inflammation and immune activation play an impor- tant role in the progression of IBS symptoms, at least in a subgroup of patients with IBS. 6 In addition, the finding that the symptoms of IBS develop after infectious acute gastroenteritis (postinfectious IBS [PI-IBS]) and in patients with inflammatory bowel disease in the remission stage implies that a dysregulated immune system plays a substantial role in the pathogenesis of IBS. 7 A localized and systemic immune response—which is associated with the recruitment of a higher number of immune cells (intraepithelial lymphocytes, mast cells, monocytes), cell-mediated cytokines, and chemokines—has also been reported in a subpopulation of patients with IBS. 1,8 Homeostatic balance exists between pro- and antiinflammatory cytokines in a controlled Accepted for publication January 18, 2017. http://dx.doi.org/10.1016/j.clinthera.2017.01.030 0149-2918/$- see front matter & 2017 Elsevier HS Journals, Inc. All rights reserved. ] 2017 1