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首页> 外文期刊>Cytokine >Inflammatory intestinal damage induced by 5-fluorouracil requires IL-4
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Inflammatory intestinal damage induced by 5-fluorouracil requires IL-4

机译：5-氟尿嘧啶引起的炎症性肠损伤需要IL-4

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摘要

Background: 5-Fluorouracil (5-FU) induces intestinal mucositis, which is characterized by epithelial ulcerations in the mucosa and clinical manifestations, such as pain and dyspeptic symptoms. Cytokines participate in the inflammatory and functional events of intestinal mucositis. IL-4 is an important mediator of intestinal inflammation, with either anti-inflammatory or pro-inflammatory functions, depending on the model of intestinal inflammation. This study aimed to evaluate the role of IL-4 in 5-FU-induced intestinal mucositis. Methods: IL-4+/+ or IL-4-/- mice (25-30g) were intraperitoneally injected with 5-FU (450mg/Kg) or saline (C). After 3days, the mice were sacrificed and the duodenum was evaluated for epithelial damage, MPO activity and cytokine concentration. Results: 5-FU induced significant damage in the intestinal epithelium of IL-4+/+ mice (reduction in the villus/crypt ratio: control=3.31±0.21μm, 5-FU=0.99±0.10μm). However, the same treatment did not induce significant damage in IL-4-/- mice (5-FU=2.87±0.19μm) compared to wild-type mice. 5-FU-induced epithelial damage increased the MPO activity (neutrophil number) and the level of pro-inflammatory cytokines (IL-4, TNF-α, IL-1β and CXCL-8) in the duodenum. These results were not observed in IL-4-/- mice treated with 5-FU. Conclusion: Our data suggest that IL-4 participates as a pro-inflammatory cytokine in a 5-FU-induced intestinal damage model and suggests that IL-4 antagonists may be novel therapeutics for this condition.
机译：背景：5-氟尿嘧啶（5-FU）诱发肠粘膜炎，其特征在于粘膜上皮溃疡和临床表现，例如疼痛和消化不良症状。细胞因子参与肠粘膜炎的炎症和功能事件。 IL-4是肠道炎症的重要介质，具有抗炎或促炎功能，具体取决于肠道炎症的模型。这项研究旨在评估IL-4在5-FU诱导的肠道粘膜炎中的作用。方法：对IL-4 + / +或IL-4-/-小鼠（25-30g）腹腔注射5-FU（450mg / Kg）或生理盐水（C）。 3天后，处死小鼠并评估十二指肠的上皮损伤，MPO活性和细胞因子浓度。结果：5-FU诱导了IL-4 + / +小鼠肠道上皮的显着损伤（绒毛/隐窝比率降低：对照组= 3.31±0.21μm，5-FU = 0.99±0.10μm）。然而，与野生型小鼠相比，相同的治疗对IL-4-/-小鼠（5-FU = 2.87±0.19μm）没有引起明显的损伤。 5-FU诱导的上皮损伤增加了十二指肠的MPO活性（中性粒细胞数）和促炎性细胞因子（IL-4，TNF-α，IL-1β和CXCL-8）的水平。在用5-FU治疗的IL-4-/-小鼠中未观察到这些结果。结论：我们的数据表明IL-4作为促炎细胞因子参与5-FU诱导的肠道损伤模型，并提示IL-4拮抗剂可能是针对这种情况的新型治疗方法。

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