Work

Effect of Rvd2 on Experimental Colitis Is Associated With the Activation of the Anti-inflammatory Cytokine Il10

Year: 2024

Type: article

Abstract: Introduction New therapeutic strategies targeting the inflammatory process are being proposed for inflammatory bowel diseases (IBD), as clinical failure remains a challenge in managing these patients. Recent studies have highlighted the role of specialized pro-resolving lipid mediators (SPMs) in the active resolution of chronic inflammation. This study aimed to investigate how the effect of Resolvin D2 (RvD2) on dextran sodium sulfate (DSS)-induced experimental colitis occurs. Method An experimental model was conducted using male C57BL/6J mice and IL10 knockout (KO) animals. Following the induction of DSS-induced experimental colitis, animals were subdivided and treated with RvD2 or anti-TNFα. The metabolic phenotype and inflammatory profile of these animals were assessed through real-time PCR, ELISA, CBA multiplex, and histology. The study was approved by the Animal Use Ethics Committee. Results A reduction in colon length and progressive weight loss were observed in the IL10 KO groups with DSS-induced experimental colitis (p < 0.0001) and in the IL10 KO group with DSS-induced experimental colitis treated with RvD2 (p < 0.0001) compared to the non-colitic IL10 KO group. IL10 KO mice with DSS-induced experimental colitis and IL10 KO mice treated with RvD2 developed severe colitis characterized by weight loss by day 11 of exposure (p < 0.05). The mice exhibited soft to liquid stools with blood, which, along with weight variation, increased the Disease Activity Index and colon shortening. Additionally, significant increases in IL1B were observed in colon samples from IL10 KO mice with DSS-induced colitis, regardless of RvD2 treatment (p < 0.05). Significant increases in IL6 (p < 0.01) and IL17 (p < 0.05) were observed in the IL10 KO DSS group, alongside a reduction in interferon-gamma (p < 0.05) when compared to the non-colitic IL10 KO group. None of the evaluated cytokines decreased significantly in IL10 KO DSS mice treated with RvD2 compared to untreated ones. Conclusion IL10 KO animals did not exhibit a significant reduction in pro-inflammatory cytokines following RvD2 treatment, demonstrating that the beneficial effect of this mediator on experimental colitis occurs via IL10. Publication History Article published online: 25 April 2025 © 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/) Thieme Revinter Publicações Ltda. Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

Source: Journal of Coloproctology

DOI: 10.1055/s-0045-1808717