Commonality of the IL-4/IL-13 pathway in atopic diseases

被引:355
|
作者
Gandhi, Namita A. [1 ]
Pirozzi, Gianluca [2 ]
Graham, Neil M. H. [3 ]
机构
[1] Regeneron Pharmaceut Inc, Clin Sci, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA
[2] Sanofi, Res & Dev, Bridgewater, NJ USA
[3] Regeneron Pharmaceut Inc, Project Direct, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA
关键词
interleukin-4; interleukin-13; dupilumab; lebrikizumab; tralokinumab; Type; 2; pathway; asthma; atopic dermatitis; nasal polyposis; ACTIVATION-REGULATED CHEMOKINE; DOUBLE-BLIND; PERSISTENT ASTHMA; ADULT PATIENTS; SERUM THYMUS; INTERLEUKIN-4; RECEPTOR; ORAL CYCLOSPORINE; ALLERGIC DISEASES; STRUCTURAL BASIS; CLUSTER-ANALYSIS;
D O I
10.1080/1744666X.2017.1298443
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Introduction: Allergy results from an aberrant Type 2 inflammatory response, triggered by a wide range of environmental antigens (allergens) that lead to various immune responses, culminating in the production of immunoglobulin E (IgE). Two key cytokines, interleukin (IL)-4 and IL-13, are critical to the induction and perpetuation of the Type 2 response, and have been implicated in multiple atopic diseases.Area covered: This review summarizes recent milestone developments that have elucidated components of the pathogenesis of atopic diseases such as atopic dermatitis (AD), asthma, and chronic sinusitis with nasal polyposis (CSwNP).Expert commentary: Several therapeutic agents that selectively target potentiators of the Type 2 pathway have shown efficacy in one or more of these atopic diseases, but few agents have proven to be broadly applicable across all three atopic diseases. Dupilumab, a human monoclonal antibody that simultaneously inhibits signaling of IL-4 and IL-13, has demonstrated significant clinical efficacy in AD, asthma, and CSwNP. The fact that these diseases often occur as comorbidities and respond to the same therapy suggests that there is a common underlying pathogenic pathway, and that IL-4 and IL-13 cytokines are central to regulating the pathogenesis of these atopic diseases.
引用
收藏
页码:425 / 437
页数:13
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