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病例报告:1例肠白塞病在用英夫利昔单抗治疗后白细胞介素-6和叉头框蛋白P3信使核糖核酸表达增强

Case Report: A Case of Intestinal Behçet's Disease Exhibiting Enhanced Expression of IL-6 and Forkhead Box P3 mRNA After Treatment With Infliximab.

作者信息

Yoshikawa Keisuke, Watanabe Tomohiro, Sekai Ikue, Takada Ryutaro, Hara Akane, Kurimoto Masayuki, Masuta Yasuhiro, Otsuka Yasuo, Yoshikawa Tomoe, Masaki Sho, Kamata Ken, Minaga Kosuke, Komeda Yoriaki, Chikugo Takaaki, Kudo Masatoshi

机构信息

Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.

Department of Diagnostic Pathology, Kindai University Hospital, Osaka, Japan.

出版信息

Front Med (Lausanne). 2021 May 14;8:679237. doi: 10.3389/fmed.2021.679237. eCollection 2021.

Abstract

Behçet's disease (BD) is a rare inflammatory condition characterized by oral and genital ulcers, skin lesions, as well as ophthalmological, neurological, and gastrointestinal manifestations. BD involving the gastrointestinal tract is known as intestinal BD. The mucosa of the gastrointestinal tract of patients with intestinal BD exhibits enhanced levels of proinflammatory cytokines, such as IL-1β, IL-6, and TNF-α. These proinflammatory cytokines play pathogenic roles in the development of BD, as evidenced by the fact that biologics targeting these cytokines effectively induce BD remission. It should be noted, however, that the molecular mechanisms by which the blockade of these cytokines suppresses chronic inflammatory responses in BD are poorly understood. Herein, we report a case of intestinal BD resistant to prednisolone that was successfully treated with infliximab (IFX). The induction of remission by IFX was accompanied by a marked elevation of IL-6 and forkhead box P3 (FOXP3) at mRNA level. This case suggests that induction of remission by IFX is mediated not only by the suppression of TNF-α-mediated signaling pathways, but also by the promotion of IL-6 expression and accumulation of regulatory T cells expressing FOXP3.

摘要

白塞病(BD)是一种罕见的炎症性疾病,其特征为口腔和生殖器溃疡、皮肤病变以及眼科、神经科和胃肠道表现。累及胃肠道的BD被称为肠道白塞病。肠道白塞病患者的胃肠道黏膜中促炎细胞因子水平升高,如白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)。这些促炎细胞因子在BD的发病过程中起致病作用,靶向这些细胞因子的生物制剂能有效诱导BD缓解即证明了这一点。然而,应该注意的是,这些细胞因子的阻断抑制BD慢性炎症反应的分子机制尚不清楚。在此,我们报告一例对泼尼松龙耐药的肠道白塞病患者,该患者用英夫利昔单抗(IFX)成功治疗。IFX诱导缓解伴随着IL-6和叉头框P3(FOXP3)在mRNA水平的显著升高。该病例表明,IFX诱导缓解不仅是通过抑制TNF-α介导的信号通路,还通过促进IL-6表达和表达FOXP3的调节性T细胞的积累来实现的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fc6/8160115/0d07af2e8c50/fmed-08-679237-g0001.jpg

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