Co-administration of 1,25-dihydroxyvitamin D3 and infliximab improves colitis in mice by modulating Treg differentiation.

IF 2.1 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Iranian Journal of Basic Medical Sciences Pub Date : 2024-01-01 DOI:10.22038/IJBMS.2024.74640.16209
Yan Hu, Yang Wang, Ying Chen, ChuanYing Li, Yun Long, Cheng Wu
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Abstract

Objectives: The combination of TNF-α inhibitors and vitamin D in colitis remains to be elucidated. In the present study, we revealed the benefit of infliximab (IFX) and vitamin D in a mouse model of Ulcerative colitis (UC).

Materials and methods: A dextran sulfate sodium-induced colitis model was used. The therapeutic effect of the combination was evaluated by symptom and histopathology analysis. The synergistic mechanism was explored by detecting the regulatory effect of the combined therapy on Regulatory T cell (Treg) differentiation.

Results: IFX and 1,25-dihydroxyvitamin D3 (VitD3) synergistically prevented the development of colitis by improving clinical signs, pathological and hematological manifestation, and inhibiting intestinal inflammation (decreasing TNF-α, IL-1β, and IL-6). Co-administration of IFX (2.5 mg/kg) with VitD3 or IFX (5.0 mg/kg) with VitD3 was more effective than administration of IFX (2.5 mg/kg, 5.0 mg/kg). There was no difference in therapeutic effect between IFX (5.0 mg/kg) and VitD3+ IFX (2.5 mg/kg) groups or between the VitD3+IFX (5.0 mg/kg) and VitD3+ Azathioprine (AZA) groups. VitD3 or combination therapy showed more powerful regulation of splenetic Treg differentiation and IL-10 production than IFX alone. Moreover, VitD3 alone or in combination induced higher levels of Foxp3 and IL-10 than IFX in colon tissue. In ulcerative colitis patients, serum VitD3 levels positively correlated with Treg levels.

Conclusion: VitD3 and IFX synergistically inhibit colitis based on their powerful regulation of Treg differentiation. VitD3 combined with IFX is an alternative therapy for patients who are intolerant to standard doses of IFX or combination of IFX and AZA.

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同时服用 1,25-二羟维生素 D3 和英夫利昔单抗可通过调节 Treg 分化改善小鼠结肠炎。
目的:TNF-α抑制剂和维生素D在结肠炎中的联合应用仍有待阐明。本研究揭示了英夫利昔单抗(IFX)和维生素 D在溃疡性结肠炎(UC)小鼠模型中的益处:采用葡聚糖硫酸钠诱导的结肠炎模型。材料和方法:采用葡聚糖硫酸钠诱导的结肠炎模型,通过症状和组织病理学分析评估联合疗法的治疗效果。通过检测联合疗法对调节性 T 细胞(Treg)分化的调节作用来探索协同机制:结果:IFX和1,25-二羟维生素D3(VitD3)通过改善临床症状、病理和血液学表现以及抑制肠道炎症(降低TNF-α、IL-1β和IL-6)协同预防结肠炎的发展。IFX(2.5 毫克/千克)与 VitD3 联合用药或 IFX(5.0 毫克/千克)与 VitD3 联合用药比 IFX(2.5 毫克/千克、5.0 毫克/千克)用药更有效。IFX(5.0 毫克/千克)组与 VitD3+ IFX(2.5 毫克/千克)组之间或 VitD3+IFX(5.0 毫克/千克)组与 VitD3+ 硫唑嘌呤(AZA)组之间的治疗效果没有差异。与单用IFX相比,VitD3或联合疗法对脾Treg分化和IL-10产生的调节作用更强。此外,在结肠组织中,VitD3单独或联合疗法诱导的Foxp3和IL-10水平高于IFX。在溃疡性结肠炎患者中,血清VitD3水平与Treg水平呈正相关:结论:VitD3 和 IFX 能协同抑制结肠炎,因为它们能有效调节 Treg 的分化。对于不能耐受标准剂量 IFX 或 IFX 与 AZA 联用的患者,VitD3 与 IFX 联用是一种替代疗法。
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来源期刊
Iranian Journal of Basic Medical Sciences
Iranian Journal of Basic Medical Sciences MEDICINE, RESEARCH & EXPERIMENTAL-PHARMACOLOGY & PHARMACY
CiteScore
4.00
自引率
4.50%
发文量
142
审稿时长
6-12 weeks
期刊介绍: The Iranian Journal of Basic Medical Sciences (IJBMS) is a peer-reviewed, monthly publication by Mashhad University of Medical Sciences (MUMS), Mashhad, Iran . The Journal of "IJBMS” is a modern forum for scientific communication. Data and information, useful to investigators in any discipline in basic medical sciences mainly including Anatomical Sciences, Biochemistry, Genetics, Immunology, Microbiology, Pathology, Pharmacology, Pharmaceutical Sciences, and Physiology, will be published after they have been peer reviewed. This will also include reviews and multidisciplinary research.
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