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银屑病的新型治疗方法包括白细胞介素 23 抑制剂、磷酸二酯酶 4 抑制剂和 Janus 激酶抑制剂。

Newer treatments of psoriasis regarding IL-23 inhibitors, phosphodiesterase 4 inhibitors, and Janus kinase inhibitors.

机构信息

Department of Skin Structural Studies, Chair of Cosmetology, School of Pharmacy with Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Poland.

Department of Dermatology, Andrzej Mielęcki Memorial Independent Public Clinical Hospital in Katowice, Poland.

出版信息

Dermatol Ther. 2017 Nov;30(6). doi: 10.1111/dth.12555. Epub 2017 Oct 10.

Abstract

The rapid progress of genetic engineering furthermore opens up new prospects in the therapy of this difficult-to-treat disease. IL-23 inhibitors, phosphodiesterase 4 (PDE4) inhibitors, and Janus kinase (JAK) inhibitors are currently encouraging further research. Two drugs which are IL-23 inhibitors are now in phase III of clinical trials. The aim of the action of both drugs is selective IL-23 inhibition by targeting the p19 subunit. Guselkumab is a fully human monoclonal antibody. Tildrakizumab is a humanized monoclonal antibody, which also belongs to IgG class and is targeted to subunit p19 of interleukin 23 (IL-23). Phosphodiesterase inhibitors exert an anti-inflammatory action and their most common group is the PDE4 family. PDE4 inhibits cAMP, which reduces the inflammatory response of the pathway of Th helper lymphocytes, Th17, and type 1 interferon which modulates the production of anti-inflammatory cytokines such as IL-10 interleukins. The Janus kinase (JAK) signaling pathway plays an important role in the immunopathogenesis of psoriasis. Tofacitinib suppresses the expression of IL-23, IL-17A, IL-17F, and IL-22 receptors during the stimulation of lymphocytes. Ruxolitinib is a selective inhibitor of JAK1 and JAK2 kinases and the JAK-STAT signaling pathway. This article is a review of the aforementioned drugs as described in the latest available literature.

摘要

基因工程的快速发展为这种难以治疗的疾病的治疗开辟了新的前景。IL-23 抑制剂、磷酸二酯酶 4 (PDE4) 抑制剂和 Janus 激酶 (JAK) 抑制剂目前正在鼓励进一步的研究。两种 IL-23 抑制剂药物目前正在进行 III 期临床试验。这两种药物的作用目的都是通过靶向 p19 亚基选择性抑制 IL-23。古塞库单抗是一种完全人源单克隆抗体。替度鲁单抗是一种人源化单克隆抗体,也属于 IgG 类,靶向白细胞介素 23 (IL-23) 的 p19 亚基。磷酸二酯酶抑制剂发挥抗炎作用,最常见的是 PDE4 家族。PDE4 抑制 cAMP,从而减少 Th 辅助淋巴细胞、Th17 和 1 型干扰素途径的炎症反应,调节抗炎细胞因子如 IL-10 白细胞介素的产生。Janus 激酶 (JAK) 信号通路在银屑病的免疫发病机制中起着重要作用。托法替尼在淋巴细胞刺激过程中抑制 IL-23、IL-17A、IL-17F 和 IL-22 受体的表达。鲁索利替尼是 JAK1 和 JAK2 激酶以及 JAK-STAT 信号通路的选择性抑制剂。本文综述了上述药物,这些药物是根据最新的可用文献描述的。

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