Interleukin-4 (IL-4) and
interleukin-13 (IL-13) are key
cytokines involved in the pathophysiology of both immune-inflammatory and structural changes underlying type 2
asthma.
IL-4 plays a pivotal role in Th2 cell polarization,
immunoglobulin E (
IgE) synthesis and eosinophil recruitment into the airways.
IL-13 synergizes with
IL-4 in inducing
IgE production and also promotes
nitric oxide (NO) synthesis, eosinophil chemotaxis, bronchial hyperresponsiveness and mucus secretion, as well as the proliferation of airway resident cells such as fibroblasts and smooth muscle cells. The biological effects of
IL-4 and
IL-13 are mediated by complex signaling mechanisms activated by receptor dimerization triggered by
cytokine binding to the α-subunit of the
IL-4 receptor (IL-4Rα). The fully human
IgG4 monoclonal antibody dupilumab binds to IL-4Rα, thereby preventing its interactions with both
IL-4 and
IL-13. This mechanism of action makes it possible for
dupilumab to effectively inhibit type 2
inflammation, thus significantly reducing the exacerbation of severe
asthma, the consumption of oral
corticosteroids (OCS) and the levels of fractional exhaled NO (FeNO).
Dupilumab has been approved not only for the add-on
therapy of severe
asthma, but also for the biological treatment of
atopic dermatitis and nasal polyposis.