Targeting key proximal drivers of type 2 inflammation in disease

Nat Rev Drug Discov. 2016 Jan;15(1):35-50. doi: 10.1038/nrd4624. Epub 2015 Oct 16.


Systemic type 2 inflammation encompassing T helper 2 (TH2)-type responses is emerging as a unifying feature of both classically defined allergic diseases, such as asthma, and a range of other inflammatory diseases. Rather than reducing inflammation with broad-acting immunosuppressants or narrowly targeting downstream products of the TH2 pathway, such as immunoglobulin E (IgE), efforts to target the key proximal type 2 cytokines - interleukin-4 (IL-4), IL-5 and IL-13 - represent a promising strategy to achieve therapeutic benefit across multiple diseases. After several initial disappointing clinical results with therapies targeting IL-4, IL-5 or IL-13 in asthma, applying a personalized approach achieved therapeutic benefit in an asthma subtype exhibiting an 'allergic' phenotype. More recently, efficacy was extended into a broad population of people with asthma. This argues that the Type 2 inflammation is broadly relevant across the severe asthma population if the key upstream drivers are properly blocked. Moreover, the simultaneous inhibition of IL-4 and IL-13 has shown significant clinical activity in diseases that are often co-morbid with asthma - atopic dermatitis and chronic sinusitis with nasal polyps - supporting the hypothesis that targeting a central 'driver pathway' could benefit multiple allergic diseases.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / immunology*
  • Interleukin-13 / antagonists & inhibitors
  • Interleukin-13 / immunology
  • Interleukin-4 / antagonists & inhibitors
  • Interleukin-4 / immunology
  • Interleukin-5 / antagonists & inhibitors
  • Interleukin-5 / immunology
  • Models, Immunological
  • Molecular Targeted Therapy / methods*
  • T-Lymphocytes, Helper-Inducer / drug effects*
  • T-Lymphocytes, Helper-Inducer / immunology*


  • Antibodies, Monoclonal
  • Interleukin-13
  • Interleukin-5
  • Interleukin-4