特应性皮炎
封锁
炎症
重组DNA
细胞因子
免疫学
医学
巨噬细胞
生物
内科学
受体
基因
生物化学
体外
作者
Young‐Saeng Jang,Kyungsun Lee,Mi-Hyun Park,Jin Joo Park,Gil Soon Choi,Chohee Kim,Shima Barati Dehkohneh,Susan Chi,Jaekyu Han,Moo Young Song,Yong‐Hyun Han,Sang-Hoon Cha,Seung Goo Kang
出处
期刊:Cytokine
[Elsevier]
日期:2023-12-01
卷期号:172: 156413-156413
标识
DOI:10.1016/j.cyto.2023.156413
摘要
Given the clinical success of cytokine blockade in managing diverse inflammatory human conditions, this approach could be exploited for numerous refractory or uncontrolled inflammatory conditions by identifying novel targets for functional blockade. Interleukin (IL)-18, a pro-inflammatory cytokine, is relatively underestimated as a therapeutic target, despite accumulated evidence indicating the unique roles of IL-18 in acute and chronic inflammatory conditions, such as macrophage activation syndrome. Herein, we designed a new form of IL-18 blockade, i.e., APB-R3, a long-acting recombinant human IL-18BP linked to human albumin-binding Fab fragment, SL335, for extending half-life. We then explored the pharmacokinetics and pharmacodynamics of APB-R3. In addition to an extended serum half-life, APB-R3 alleviates liver inflammation and splenomegaly in a model of the macrophage activation syndrome induced in IL-18BP knockout mice. Moreover, APB-R3 substantially controlled skin inflammation in a model of atopic dermatitis. Thus, we report APB-R3 as a new potent IL-18 blocking agent that could be applied to treat IL-18-mediated inflammatory diseases.
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