IL-4 and IL-13 Have Shared and Distinct Roles in Type 2 Inflammation1

IL-4 perpetuates the type 2 inflammatory cascade and its effects through a positive feedback loop2-5

Both IL-4 and IL-13 are key mediators of type 2 inflammation and impact skin barrier dysfunction2-5:

  • Initial and continued Th2 differentiation and expansion2
IL-4 and IL-13
  • B cell class switching and IgE production2-4
  • Increase vascular adhesion and permeability3,6,7
  • Production of chemoattractants for inflammatory trafficking3,4
  • The itch-scratch cycle3,4
  • Induced barrier defects3-5

ILC2, type 2 innate lymphoid cells.


DUPIXENT Helps Repair the Skin by Targeting a Key Source of Type 2 Inflammation1,8-10

DUPIXENT works beneath the skin’s surface, specifically targeting IL-4 and IL-13 signaling to1,8,9:

  • Reduce epidermal hyperplasia
  • Modify lesional skin appearance
  • Modulate genes related to epidermal pathology in atopic dermatitis

DUPIXENT is NOT an immunosuppressant or a steroid8

Watch the video to see how it works.


Atopic dermatitis, or AD, is a chronic inflammatory skin disease that leads to dry, scaly, itchy skin and eczematous lesions. Moderate-to-severe AD is a potentially debilitating disease. The pathophysiology of AD is complex and multifactorial, involving immune and epidermal barrier components influenced by genetic and environmental factors. Patients with AD have a mix of lesional and nonlesional skin.

Though normal looking, nonlesional skin has persistent underlying inflammation due to activation of the immune system. In patients with AD, there are 2 main converging pathophysiological features: increased skin inflammation coupled with abnormalities of epidermal barrier structures and function.

Antigens are recognized by resident cells such as Langerhans cells and innate lymphoid type 2 cells and are presented to T cells in the skin and in lymph nodes driving immune inflammatory response in AD. This results in the initiation of a type 2, including Th2, immune response, such as IL-4, IL-13, and IL-31 release of chemokines. Cytokines that were historically known as Th2 cytokines, such as IL-4 and IL-13, are also produced by other cell types, including ILC2s, eosinophils, mast cells, basophils, and macrophages and are thus now known as type 2 cytokines.

In the acute phase of lesion development there is an increase in T cells and continued release of the type 2 cytokines IL-4 and IL-13, along with other cytokines and chemokines that promote inflammation. As the lesion progresses due to chronic disease, there is persistent type 2, including Th2, signaling. IL-4 and IL-13 are cytokines involved in the development of AD and play roles in the regulation of the immune response. IL-4 and IL-13 signal mainly through 2 receptor complexes.

The Type I receptor, consisting of IL-4Rα and γ-chain subunits, only binds IL-4. The Type II receptor, consisting of IL-4Rα and IL-13Rα1 subunits, is the primary receptor for IL-13 but also binds IL-4. In AD, increased levels of IL-4 and IL-13 lead to amplified signaling of type 2 cytokines and chemokines and activation of subsequent proinflammatory signaling pathways.

Dupilumab is a human monoclonal antibody that binds specifically to the IL-4Rα subunit of the receptor complexes for IL-4 and IL-13, two type 2 cytokines that play roles in the pathogenesis of AD. Dupilumab inhibits IL-4 signaling via the Type I receptor and both IL-4 and IL-13 signaling through the Type II receptor resulting in decreased IL-4 and IL-13 cytokine-induced responses, including the release of proinflammatory cytokines, chemokines, and IgE.


Identifying DUPIXENT Patients DUPIXENT may be an appropriate treatment for patients aged 6 years and older with uncontrolled moderate-to-severe atopic dermatitis. Identify Patients
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  1. 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.
  2. Palomares O, Akdis M, Martín-Fontecha M, Akdis CA. Mechanisms of immune regulation in allergic diseases: the role of regulatory T and B cells. Immunol Rev. 2017;278(1):219-236.
  3. Weidinger S, Beck LA, Bieber T, Kabashima K, Irving AD. Atopic dermatitis. Nat Rev Dis Primers. 2018;4(1):1. doi:10.1038/s41572-018- 0001-z
  4. Rerknimitr P, Otsuka A, Nakashima C, Kabashima K. The etiopathogenesis of atopic dermatitis: barrier disruption, immunological derangement, and pruritus. Inflamm Regen. 2017;37:14. doi:10.1186/s41232-017-0044-7
  5. Brunner PM, Guttman-Yassky E, Leung DYM. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol. 2017;139(4S):S65-S76.
  6. Patel KD. Eosinophil tethering to interleukin-4–activated endothelial cells requires both P-selectin and vascular cell adhesion molecule-1. Blood. 1998;92(10):3904-3911.
  7. Chen L, Lin SX, Amin S, Overbergh L, Maggiolino G, Chan LS. VCAM-1 blockade delays disease onset, reduces disease severity and inflammatory cells in an atopic dermatitis model. Immunol Cell Biol. 2010;88(3):334-342.
  8. DUPIXENT Prescribing Information.
  9. Guttman-Yassky E, Bissonnette R, Ungar B. Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis. Allergy Clin Immunol. 2019;143(1):155-172.
  10. Callewaert C, Nakatsuji T, Knight R, et al. IL-4Rα blockade by dupilumab decreases Staphylococcus aureus colonization and increases microbial diversity in atopic dermatitis. J Invest Dermatol. 2020;140(1):191-202.e7.