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嗜酸性粒细胞性皮炎的治疗策略。

Therapeutic strategies for eosinophilic dermatoses.

机构信息

Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Institute of Pharmacology, University of Bern, Bern, Switzerland; Department of Clinical Immunology and Allergology, Sechenov University, Moscow, Russia.

出版信息

Curr Opin Pharmacol. 2019 Jun;46:29-33. doi: 10.1016/j.coph.2019.01.002. Epub 2019 Feb 10.

Abstract

Eosinophil infiltration is observed in a broad spectrum of skin diseases of various origins. Eosinophils are thought to actively contribute to pathogenesis as they are able to defend against microbes, to regulate inflammation, cause tissue damage, promote remodeling and fibrosis, and initiate pruritus. Therefore, targeting eosinophils would seem a worthwhile therapeutic approach. A promising strategy is to target the production, activation and survival of eosinophils, example with antibodies directed against IL-5 or its receptor, and Siglec-8. Dexpramipexole and tyrosine kinase inhibitors have been shown to reduce eosinophil numbers in patients with hypereosinophilia. Janus kinase inhibitors block signal transduction and thus activation of inflammatory cells including eosinophils. A further approach is to target cells and cytokines acting on or mediators released by eosinophils, for example, CD52, IL-13, IL-31, TSLP, and eotaxins. This review summarizes current therapeutic strategies, including novel agents affecting eosinophils directly that are under clinical investigation.

摘要

嗜酸性粒细胞浸润可见于各种来源的广泛的皮肤疾病中。人们认为嗜酸性粒细胞能够积极参与发病机制,因为它们能够抵御微生物、调节炎症、引起组织损伤、促进重塑和纤维化,并引发瘙痒。因此,针对嗜酸性粒细胞似乎是一种有价值的治疗方法。一种有前途的策略是针对嗜酸性粒细胞的产生、激活和存活,例如使用针对白细胞介素 5 或其受体和 Siglec-8 的抗体。德普雷米克斯和酪氨酸激酶抑制剂已被证明可减少高嗜酸性粒细胞血症患者的嗜酸性粒细胞数量。Janus 激酶抑制剂阻断信号转导,从而激活包括嗜酸性粒细胞在内的炎症细胞。另一种方法是针对作用于嗜酸性粒细胞或由嗜酸性粒细胞释放的细胞和细胞因子的调节剂,例如 CD52、白细胞介素 13、白细胞介素 31、胸腺基质淋巴细胞生成素和嗜酸性粒细胞趋化因子。这篇综述总结了目前的治疗策略,包括正在临床研究中的直接影响嗜酸性粒细胞的新型药物。

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