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IL-4, IL-13, AND IL-5 ARE KEY DRIVERS
OF TYPE 2 INFLAMMATION IN ASTHMA1,2

IL-4 and IL-13 are central mediators of allergic inflammation, eosinophilic
inflammation, and epithelial barrier dysfunction in asthma—all effects that
lead to an overactive immune response1,2

Click on the cytokines to see how they fit
into Type 2 inflammation in asthma

Adapted from Hammad H
and Lambrecht BN, 2008,1
and Robinson D et al, 2017.2

Type 2 inflammation in asthma can result in increased exacerbations and decreased lung function2

Type 2 inflammation in asthma comprises multiple pathways within the
inflammatory cascade—driven by key cytokines IL-4, IL-13, and IL-53-9

TYPE 2 INFLAMMATION

IL-4

IL-13

IL-5

Th0 cell differentiation
  • Epithelial barrier disruption
  • Goblet cell hyperplasia
  • Mucus overproduction
  • Collagen deposition
  • Airway smooth muscle thickening and hyperresponsiveness
  • Nasal polyp formation
B cell isotype switching and IgE production
Eosinophil chemotaxis (recruitment) to inflamed lung tissue
and promotion of tissue eosinophilia
Eosinophil differentiation in the bone marrow
Type 2 inflammation plays a central role in asthma pathophysiology
and contributes to mucus production, IgE synthesis, subepithelial
fibrosis, bronchial remodeling, and airway hyperresponsiveness2

ILC2, type 2 innate lymphoid cells; TSLP, thymic stromal lymphopoietin.

References: 1. Hammad H, Lambrecht BN. Dendritic cells and epithelial cells: linking innate and adaptive immunity in asthma. Nat Rev Immunol. 2008;8(3):193-204. 2. Robinson D, Humbert M, Buhl R, et al. Revisiting type 2-high and type 2-low airway inflammation in asthma: current knowledge and therapeutic implications. Clin Exp Allergy. 2017;47(2):161-175. 3. Gandhi NA, Bennett BL, Graham NMH, Pirozzi G, Stahl N, Yancopoulos GD. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016;15(1):35-50. 4. Vatrella A, Fabozzi I, Calabrese C, Maselli R, Pelaia G. Dupilumab: a novel treatment for asthma. J Asthma Allergy. 2014;7:123-130. 5. Sugita K, Steer CA, Martinez-Gonzalez I, et al. Type 2 innate lymphoid cells disrupt bronchial epithelial barrier integrity by targeting tight junctions through IL-13 in asthmatic patients. J Allergy Clin Immunol. 2018;141(1):300-310.e11. 6. Yu L, Li N, Zhang J, Jiang Y. IL-13 regulates human nasal epithelial cell differentiation via H3K4me3 modification. J Inflamm Res. 2017;10:181-188. 7. Steinke JW, Borish L. Th2 cytokines and asthma. Interleukin-4: its role in the pathogenesis of asthma, and targeting it for asthma treatment with interleukin-4 receptor antagonists. Respir Res. 2001;2(2):66-70. 8. Corren J. Role of interleukin-13 in asthma. Curr Allergy Asthma Rep. 2013;13(5):415-420. 9. Fulkerson PC, Rothenberg ME. Targeting eosinophils in allergy, inflammation and beyond. Nat Rev Drug Discov. 2013;12(2):117-129.