Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract that severely impacts patients’ quality of life. Although current therapies have improved symptom management, they often fail to alter disease progression and are associated with immunosuppressive side effects. This study evaluated the immunomodulatory potential of resolvin D2 (RvD2), a pro-resolving lipid mediator, using a murine model of colitis and the ex vivo treatment of intestinal mucosal biopsies from CD patients, comparing its effects to those of conventional anti-TNFα therapy. To determine the optimal concentration of RvD2 for application in human tissue explant cultures, an initial in vitro assay was conducted using intestinal biopsies from mice with experimentally induced colitis. The explants were treated in vitro with varying concentrations of RvD2, and 0.1 μM emerged as an effective dose. This concentration significantly reduced the transcriptional levels of TNF-α (p = 0.004) and IL-6 (p = 0.026). Intestinal mucosal biopsies from fifteen patients with CD and seven control individuals were analyzed to validate RNA-sequencing data, which revealed dysregulation in the RvD2 biosynthetic and signaling pathways. The real-time PCR confirmed an increased expression of PLA2G7 (p = 0.02) and ALOX15 (p = 0.02), while the immunohistochemical analysis demonstrated the reduced expression of the RvD2 receptor GPR18 (p = 0.04) in intestinal tissues from CD patients. Subsequently, samples from eight patients with active Crohn’s disease, eight patients in remission, and six healthy controls were used for the serum analysis of RvD2 by ELISA, in vitro treatment of intestinal biopsies with RvD2 or anti-TNF, followed by transcriptional analysis, and a multiplex assay of the explant culture supernatants. The serum analysis demonstrated elevated RvD2 levels in CD patients both with active disease (p = 0.02) and in remission (p = 0.002) compared to healthy controls. The ex vivo treatment of intestinal biopsies with RvD2 decreased IL1β (p = 0.04) and TNFα (p = 0.02) transcriptional levels, comparable to anti-TNFα therapy. Additionally, multiplex cytokine profiling confirmed a reduction in pro-inflammatory cytokines, including IL-6 (p = 0.01), IL-21 (p = 0.04), and IL-22 (p = 0.009), in the supernatant of samples treated with RvD2. Altogether, these findings suggest that RvD2 promotes the resolution of inflammation in CD and supports its potential as a promising therapeutic strategy.

Background: The coronavirus disease-19 pandemic affected millions of people and its long-term impact on the health of survivors is under evaluation. Objectives: In this study, we hypothesized that severe coronavirus disease-19 could promote long-term changes in the blood levels of hormones and growth factors known to be involved in the regulation of ageing. Methods: We evaluated 49 patients that recovered from severe COVID-19 and compared them with matched controls that were never infected by the virus. The blood levels of growth hormone, insulin-like growth factor-1, insulin, brain-derived neurotrophic factor, nerve growth factor, oxytocin, ghrelin, platelet-derived growth factor, fibroblast growth factor-1, and transforming growth factor-beta were determined using enzyme-linked immunosorbent assays. Results: After six months of recovery, patients presented reduced blood levels of growth hormone, insulin-like growth factor-1, brain-derived neurotrophic factor, and platelet-derived growth factor. Fifteen months after, the reductions in the blood levels of all four hormones/growth factors persisted. Conclusions: Our study advances the field by identifying hormones and growth factors involved in ageing that undergo persistent changes in patients that recover from severe COVID-19. Further studies could explore the potential of the identified hormones/growth factors as therapeutic targets for the late complications and accelerated ageing that may affect patients recovering from severe COVID-19.