To the editor, Itaconate (ITA) is an immunometabolite derived by activated macrophages and exhibits potential anti-inflammatory activity 1. However, the role of ITA in ulcerative colitis has not been reported yet. Here, we explored the effect of exogenous ITA on dextran sodium sulfate (DSS)-induced colitis in mice. Twelve 6-week-aged female C57BL/6J mice were used in this study. Colitis was induced by administration of 2.5 DSS (36-50 kDa, MP Biomedicals) in filter-purified drinking water ad libitum for 7 days. Throughout DSS administration, mice were treated with 200 muI of either water or 2.5 mg/kg ITA by oral gavage once a day. Colon inflammation severity was measured by body weight, disease activity index (DAI), colon length and histological scores. Administration of ITA via oral gavage aggregated colitis progression induced by DSS treatment (Fig. 1A-E), as indicated by loss of body weight (P< 0.0001), increased DAI scores (P< 0.0001), depravation of colon shortening (P = 0.014) and increased histological scores (P = 0.001). Furthermore, mouse peritoneal primary macrophages were extracted and cultured in vitro. Compared with the untreated group, ITA (5mM) significantly up-regulated the mRNA expression of TNF-alpha (P = 0.013), IL-1beta (P = 0.0004), and IL-6 (P< 0.0001) in macrophages(Fig. 1F-H). These findings showed the aggravating and pro-inflammatory effects of ITA in experimental colitis.
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