Background: Allergic diseases, such as atopic dermatitis and allergic asthma, are
associated with increased inflammation and interleukin-4 (IL-4) signaling. An inhibitor of the IL-4
receptor, dupimulab, was approved recently for dermatitis. This goal of this review is to elucidate
the mechanism and effects of IL-4 signaling.
Methods: We reviewed information available in immunology and molecular biology textbooks,
and research and review articles to accomplish our goal.
Results: The increased inflammation, in allergic diseases, is due to inflammatory cytokines
released from innate leukocytes and local tissue. The increased IL-4 signaling activates the helper
Th2 cells to release IL-4, and the allergic effects. The IL-4 binds to its receptors to activate
JAK1/JAK3 mediated nuclear translocation of the phosphorylated STAT6 dimer, which stimulates
the expression of IgE antibodies in B-cells. The released IgE stimulates the release of histamines
from mast cells, alters the expression of genes associated with fibrosis, and induces apoptosis of
epidermal or epithelial cells. The resultant IL-4 effects in allergic diseases include pruritus or
wheezing, fibrosis and/or altered expression of extracellular matrix proteins, and loss of epidermal
or epithelial barrier function.
Conclusion: The specific inhibition of the Il-4 signaling, through dupimulab that binds the IL-4 α
receptor subunit, would be effective in the specific inhibition of the allergic response in patients
with allergic dermatitis or asthma.