ArticleJournal of Crohn's & colitis2020
Deletion of IL-6 Exacerbates Colitis and Induces Systemic Inflammation in IL-10-Deficient Mice.
Article in Journal of Crohn's & colitis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 51 citations in OpenAlex.
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- Effects of Polyphenols from Oat and Oat Bran on Anti-Inflammatory Activity and Intestinal Barrier Function in Raw264.7 and Caco-2 Models.Nutrients · 2025Article
- Pre-Administration ofFoods (Basel, Switzerland) · 2025Article
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- Docosahexaenoic acid (DHA) alleviates inflammation and damage induced by experimental colitis.European journal of nutrition · 2024Article
- [Old and New Biologics and Small Molecules in Inflammatory Bowel Disease: Anti-interleukins].The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi · 2024Review
- Unveiling cytokine charge disparity as a potential mechanism for immune regulation.Cytokine & growth factor reviews · 2024Review
- Exercise mitigates a gut microbiota-mediated reduction in adult hippocampal neurogenesis and associated behaviours in rats.Translational psychiatry · 2024Article
- The role of mesenchymal stem cells in attenuating inflammatory bowel disease through ubiquitination.Frontiers in immunology · 2024Review
- Exploration of the core pathway of inflammatory bowel disease complicated with metabolic fatty liver and two-sample Mendelian randomization study of the causal relationships behind the disease.Frontiers in immunology · 2024Article
- A Narrative Review of Cytokine Networks: Pathophysiological and Therapeutic Implications for Inflammatory Bowel Disease Pathogenesis.Biomedicines · 2023Review
- Terpenes: Modulating anti-inflammatory signaling in inflammatory bowel disease.Pharmacology & therapeutics · 2023Review
- Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
aimsInterleukin 6 [IL-6] or its receptor is currently a candidate for targeted biological therapy of inflammatory bowel disease [IBD]. Thus, a comprehensive understanding of the consequences of blocking IL-6 is imperative. We investigated this by evaluating the effects of IL-6 deletion on the spontaneous colitis of IL-10-deficient mice [IL-10-/-].
methodsIL-6/IL-10 double-deficient mice [IL-6-/-/IL-10-/-] were generated and analysed for intestinal inflammation, general phenotypes and molecular/biochemical changes in the colonic mucosa compared with wild-type and IL-10-/- mice.
resultsUnexpectedly, the IL-6-/-/IL-10-/- mice showed more pronounced gut inflammation and earlier disease onset than IL-10-/- mice, both locally [colon and small bowel] and systemically [splenomegaly, ulcerative dermatitis, leukocytosis, neutrophilia and monocytosis]. IL-6-/-/IL-10-/- mice exhibited elevations of multiple cytokines [IL-1β, IL-4, IL-12, TNFα] and chemokines [MCP-1 and MIG], but not IFN-γ [Th1], IL-17A and IL-17G [Th17], or IL-22 [Th22]. FOXP3 and TGF-β, two key factors for regulatory T [Treg] cell differentiation, were significantly down-regulated in the colonic mucosa, but not in the thymus or mesenteric lymph nodes, of IL-6-/-/IL-10-/- mice. CTLA-4 was diminished while iNOS was up-regulated in the colonic mucosa of IL-6-/-/IL-10-/- mice.
conclusionIn IL-10-/- mice, complete IL-6 blockade significantly aggravates gut inflammation, at least in part by suppressing Treg/CTLA-4 and promoting the IL-1β/Th2 pathway. In addition, the double mutant exhibits signs of severe systemic inflammation. Our data define a new function of IL-6 and suggest that caution should be exercised when targeting IL-6 in IBD patients, particularly those with defects in IL-10 signalling.
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