The dual role of interleukin-6 in Crohn's disease pathophysiology.
| Autor: | Alhendi A; Division of Molecular Microbiology, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, United States., Naser SA; Division of Molecular Microbiology, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, United States. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in immunology [Front Immunol] 2023 Dec 01; Vol. 14, pp. 1295230. Date of Electronic Publication: 2023 Dec 01 (Print Publication: 2023). |
| DOI: | 10.3389/fimmu.2023.1295230 |
| Abstrakt: | Interleukin-6 (IL-6) is a key mediator cytokine of the immune response as well as a regulator of many physiological and pathological processes. In Crohn's disease (CD), cytokine imbalance rules the intestinal microenvironment and leads to chronic inflammation of the gut. Pro-inflammatory cytokines are generally upregulated in inflammatory bowel disease (IBD) including TNFα and IL-6. Consequently, drugs that target these cytokines have been long sought and approved. Despite the short-term success in treating CD patients with anti-TNFα, many patients stopped responding to treatment, which made IL-6 an alternative target to alleviate inflammation in these patients. IL-6 has long been approached as part of the therapeutic strategies to treat CD and other inflammatory disorders. Clinical trials of CD patients have targeted IL-6 signaling in different mechanisms: blocking IL-6, neutralizing IL-6 receptor (IL-6R), or trapping the soluble IL-6/IL-6R complex. These trials have faced challenges and side effects in patients with gastrointestinal perforations and ulcers, for example, all of which highlight the dual role of IL-6 during intestinal inflammation and the need for this cytokine for intestinal tissue integrity. IL-6 is involved in a complex of upstream regulators and downstream signaling cascades and maintaining a physiological level of IL-6 in the blood and in the intestine is key for achieving health and homeostasis. In this review, we describe IL-6 biology and signaling and its involvement in intestinal health and inflammation. We also discuss the current strategies for targeting IL-6 pathways in CD patients, as well as molecular regulators representing potential therapeutic targets for IL-6 attenuation. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision (Copyright © 2023 Alhendi and Naser.) |
| Databáze: | MEDLINE |
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