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

被引:378
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
相关论文
共 133 条
[1]   Localization of human interleukin 13 receptor in non-haematopoietic cells [J].
Akaiwa, M ;
Yu, B ;
Umeshita-Suyama, R ;
Terada, N ;
Suto, H ;
Koga, T ;
Arima, K ;
Matsushita, S ;
Saito, H ;
Ogawa, H ;
Furue, M ;
Hamasaki, N ;
Ohshima, K ;
Izuhara, K .
CYTOKINE, 2001, 13 (02) :75-84
[2]   Persistent asthma has an accumulative impact on the loss of smell in patients with nasal polyposis [J].
Alobid, Isam ;
Cardelus, Sara ;
Benitez, Pedro ;
Maria Guilemany, Jose ;
Roca-Ferrer, Jordi ;
Picado, Cesar ;
Bernal-Sprekelsen, Manuel ;
Mullol, Joaquim .
RHINOLOGY, 2011, 49 (05) :519-524
[3]   Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease [J].
Anderson, Gary P. .
LANCET, 2008, 372 (9643) :1107-1119
[4]   Characterization of the interaction between interleukin-13 and interleukin-13 receptors [J].
Arima, K ;
Sato, K ;
Tanaka, G ;
Kanaji, S ;
Terada, T ;
Honjo, E ;
Kuroki, R ;
Matsuo, Y ;
Izuhara, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (26) :24915-24922
[5]   Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood:: ISAAC Phases One and Three repeat multicountry cross-sectional surveys [J].
Asher, M. Innes ;
Montefort, Stephen ;
Bjorksten, Bengt ;
Lai, Christopher K. W. ;
Strachan, David P. ;
Weiland, Stephan K. ;
Williams, Hywel .
LANCET, 2006, 368 (9537) :733-743
[6]   Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients With Chronic Sinusitis and Nasal Polyposis A Randomized Clinical Trial [J].
Bachert, Claus ;
Mannent, Leda ;
Naclerio, Robert M. ;
Mullol, Joaquim ;
Ferguson, Berrylin J. ;
Gevaert, Philippe ;
Hellings, Peter ;
Jiao, Lixia ;
Wang, Lin ;
Evans, Robert R. ;
Pirozzi, Gianluca ;
Graham, Neil M. ;
Swanson, Brian ;
Hamilton, Jennifer D. ;
Radin, Allen ;
Gandhi, Namita A. ;
Stahl, Neil ;
Yancopoulos, George D. ;
Sutherland, E. Rand .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2016, 315 (05) :469-479
[7]   Dupilumab Treatment in Adults with Moderate-to-Severe Atopic Dermatitis [J].
Beck, Lisa A. ;
Thaci, Diamant ;
Hamilton, Jennifer D. ;
Graham, Neil M. ;
Bieber, Thomas ;
Rocklin, Ross ;
Ming, Jeffrey E. ;
Ren, Haobo ;
Kao, Richard ;
Simpson, Eric ;
Ardeleanu, Marius ;
Weinstein, Steven P. ;
Pirozzi, Gianluca ;
Guttman-Yassky, Emma ;
Suarez-Farinas, Mayte ;
Hager, Melissa D. ;
Stahl, Neil ;
Yancopoulos, George D. ;
Radin, Allen R. .
NEW ENGLAND JOURNAL OF MEDICINE, 2014, 371 (02) :130-139
[8]   IDENTIFICATION OF LYMPHOCYTES-T, MACROPHAGES, AND ACTIVATED EOSINOPHILS IN THE BRONCHIAL-MUCOSA IN INTRINSIC ASTHMA - RELATIONSHIP TO SYMPTOMS AND BRONCHIAL RESPONSIVENESS [J].
BENTLEY, AM ;
MENZ, G ;
STORZ, C ;
ROBINSON, DS ;
BRADLEY, B ;
JEFFERY, PK ;
DURHAM, SR ;
KAY, AB .
AMERICAN REVIEW OF RESPIRATORY DISEASE, 1992, 146 (02) :500-506
[9]   Mechanisms of disease: Atopic dermatitis [J].
Bieber, Thomas .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (14) :1483-1494
[10]   Atopic dermatitis: a disease of altered skin barrier and immune dysregulation [J].
Boguniewicz, Mark ;
Leung, Donald Y. M. .
IMMUNOLOGICAL REVIEWS, 2011, 242 :233-246