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Role of interleukin-6-mediated inflammation in the pathogenesis of inflammatory bowel disease: focus on the available therapeutic approaches and gut microbiome

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Journal of Cell Communication and Signaling Aims and scope

Abstract

Inflammatory bowel disease (IBD) is considered a chronic inflammatory and multifactorial disease of the gastrointestinal tract. Crohn’s disease (CD) and ulcerative colitis (UC) are two types of chronic IBD. Although there is no accurate information about IBD pathophysiology, evidence suggests that various factors, including the gut microbiome, environment, genetics, lifestyle, and a dysregulated immune system, may increase susceptibility to IBD. Moreover, inflammatory mediators such as interleukin-6 (IL-6) are involved in the immunopathogenesis of IBDs. IL-6 contributes to T helper 17 (Th17) differentiation, mediating further destructive inflammatory responses in CD and UC. Moreover, Th1-mediated responses participate in IBD, and the antiapoptotic IL-6/IL-6 receptor (IL-6R)/signal transducer and activator of transcription 3 (STAT3) signals are responsible for preserving Th1 cells in the site of inflammation. It has been revealed that fecal bacteria isolated from UC-active and UC-remission patients stimulate the hyperproduction of several cytokines, such as IL-6, tumor necrosis factor-α (TNF-α), IL-10, and IL-12. Given the importance of the IL-6/IL-6R axis, various therapeutic options exist for controlling or treating IBD. Therefore, alternative therapeutic approaches such as modulating the gut microbiome could be beneficial due to the failure of the target therapies so far. This review article summarizes IBD immunopathogenesis focusing on the IL-6/IL-6R axis and discusses available therapeutic approaches based on the gut microbiome alteration and IL-6/IL-6R axis targeting and treatment failure.

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Mashhad University of Medical Sciences supported this study.

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  1. Department of Laboratory Sciences, School of Allied Medical Sciences, Arak University of Medical Sciences, Arak, Iran

    Arshia Shahini

  2. Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Ali Shahini

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Shahini, A., Shahini, A. Role of interleukin-6-mediated inflammation in the pathogenesis of inflammatory bowel disease: focus on the available therapeutic approaches and gut microbiome. J. Cell Commun. Signal. 17, 55–74 (2023). https://doi.org/10.1007/s12079-022-00695-x

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  • DOI: https://doi.org/10.1007/s12079-022-00695-x

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