淋巴细胞功能相关抗原-1拮抗剂 Lifitegrast 对银屑病有显著疗效

IF 3.5 4区 医学 Q2 CHEMISTRY, MEDICINAL Drug Development Research Pub Date : 2024-12-16 DOI:10.1002/ddr.70034
Rahul Sudhakar Gawande, Lakshmi Rao Thakkalapally, Anil M. Pethe
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引用次数: 0

摘要

lifitgrast是一种淋巴细胞功能相关抗原-1 (LFA-1)拮抗剂,被批准用于治疗干眼症。本研究探讨了利替格司特对咪喹莫特诱导的小鼠银屑病模型的影响。对利替格司特(5%溶液)在吡喹莫德致C57小鼠银屑病模型中的作用进行了试验。将lifitgrast局部给予银屑病皮肤,每天2次,持续6天,评估表皮皮肤厚度、银屑病面积和严重程度指数(PASI)评分以及炎症标志物。利替格司特抑制吡喹莫德诱导的表皮厚度、组织病理学改变和PASI评分的增加。银屑病炎症的减轻伴随着皮肤中TNF-α、IL-6、IL-22和IL-17/IL-23轴基因表达的降低,其效果与口服环孢素A(5 mg/kg,每日2次)治疗相当。Lifitegrast显示出显著的抗炎活性,主要是通过降低银屑病相关细胞因子基因表达,降低体内银屑病的严重程度。LFA-1和ICAM-1拮抗剂的显著作用表明银屑病是一种新的局部治疗方法。
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Lifitegrast, a Lymphocyte Function-Associated Antigen-1 Antagonist Demonstrates Beneficial Effect in Psoriasis

Lifitegrast is a lymphocyte function-associated antigen-1 (LFA-1) antagonist, which is approved for treatment of dry eye disease. In this work we explored the effect of lifitegrast in imiquimod induced psoriasis model in mice. Lifitegrast (5% solution) was tested in imiquimod-induced psoriasis model in C57 mice. Lifitegrast was topically administered twice a day to the psoriatic skin for 6 days and epidermal skin thickness, psoriasis area and severity index (PASI) score and inflammation markers were assessed. Lifitegrast inhibited the imiquimod-induced increase in the epidermal thickness, histopathological changes and PASI score. This decrease in psoriasis inflammation was accompanied by decrease in TNF-α, IL-6, IL-22 and IL-17/IL-23 axis gene expression in the skin, and the effect is comparable to the oral cyclosporine A(5 mg/kg, twice a day) treatment. Lifitegrast demonstrated significant anti-inflammatory activity, mainly through reduction in cytokine gene expression related to psoriasis and decreased the severity of psoriasis in vivo. The significant effect shown by this LFA-1 and ICAM-1 antagonist indicates a novel topical treatment for psoriasis.

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来源期刊
CiteScore
6.40
自引率
2.60%
发文量
104
审稿时长
6-12 weeks
期刊介绍: Drug Development Research focuses on research topics related to the discovery and development of new therapeutic entities. The journal publishes original research articles on medicinal chemistry, pharmacology, biotechnology and biopharmaceuticals, toxicology, and drug delivery, formulation, and pharmacokinetics. The journal welcomes manuscripts on new compounds and technologies in all areas focused on human therapeutics, as well as global management, health care policy, and regulatory issues involving the drug discovery and development process. In addition to full-length articles, Drug Development Research publishes Brief Reports on important and timely new research findings, as well as in-depth review articles. The journal also features periodic special thematic issues devoted to specific compound classes, new technologies, and broad aspects of drug discovery and development.
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