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Review
. 2025 Mar;15(3):579-597.
doi: 10.1007/s13555-025-01352-y. Epub 2025 Feb 10.

Interleukin-4 and Atopic Dermatitis: Why Does it Matter? A Narrative Review

Tiago Torres  1   2 , Pedro Mendes-Bastos  3 , Maria J Cruz  4   5 , Bruno Duarte  6 , Paulo Filipe  7 , Maria J P Lopes  6   8   9 , Margarida Gonçalo  10   11
Affiliations
Review

Interleukin-4 and Atopic Dermatitis: Why Does it Matter? A Narrative Review

Tiago Torres et al. Dermatol Ther (Heidelb). 2025 Mar.

Abstract

Atopic dermatitis (AD) is a common chronic inflammatory skin condition that significantly impairs patients' quality of life as a result of intense itching and persistent eczematous lesions. Although AD has a multifaceted etiology-including genetic predisposition, environmental triggers, barrier dysfunction, and dysregulated immune responses-interleukin-4 (IL-4) has a recognized central role in its pathogenesis. This narrative review explores the role of IL-4 in the pathophysiology of AD, its contribution to the atopic march, and the therapeutic impact of IL-4 inhibition. IL-4 plays a critical role in skin barrier dysfunction, dysbiosis, pruritus, and inflammation, all of which contribute to the debilitating symptoms of AD. Moreover, IL-4 is implicated in other atopic conditions, such as asthma, allergic rhinitis, and food allergies, underscoring its role beyond AD and its importance in the atopic march. Recent advances in targeted therapies, particularly IL-4/IL-13 signaling inhibitors, have changed AD management. Dupilumab, an IL-4 receptor antagonist, has demonstrated significant efficacy in reducing AD symptoms and enhancing patient outcomes in both children and adults. In addition to symptomatic relief, suppressing IL-4 signaling may also offer potential for disease modification, altering AD's progression and possibly preventing the onset of other atopic conditions. This review highlights the crucial role of IL-4 as a therapeutic target in AD. By understanding the role of IL-4 in AD pathogenesis and exploring the therapeutic implications of targeting IL-4 pathways, this work can contribute to guide future research concerning treatment approaches and also emphasize the need for early and targeted interventions to mitigate disease impact and ultimately improve patient quality of life.

Keywords: Atopic dermatitis; Atopic march; Disease modification; Dysbiosis; Inflammation; Interleukin-4; Pruritus; Skin barrier dysfunction; Targeted therapies; Th2 inflammation.

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Conflict of interest statement

Declarations. Conflict of Interest: Tiago Torres has received consultancy and/or speaker’s honoraria from and/or participated in clinical trials sponsored by AbbVie, Amgen, Almirall, Amgen, Apogee Therapeutics, Arena Pharmaceuticals, Biocad, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Fresenius-Kabi, Johnson & Johnson Innovative Medicine, LEO Pharma, Eli Lilly, MSD, Mylan, Novartis, Pfizer, Samsung-Bioepis, Sanofi-Genzyme, Sandoz, STADA and UCB. Tiago Torres is also an Editorial Board member of Dermatology and Therapy. Tiago Torres was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Pedro Mendes-Bastos has received consultancy and/or speaker’s honoraria from and/or participated in clinical trials sponsored by Lilly, AbbVie, Janssen, Novartis, LEO Pharma, Almirall, Sanofi, Regeneron, Viatris, Pierre Fabre, L’Oréal, Organon, Evelo Biosciences, CS Portugal, Pfizer, Biogen, Apogee, Amgen. Margarida Gonçalo has participated in clinical trials, advisory board and/or lectures promoted by Abbvie, Almirall, Amgen, AstraZeneca, Biogen, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi-Genzyme, Takeda. Maria João Cruz has participated in clinical trials, advisory board and/or lectures promoted by Abbvie, Almirall, Amgen, Janssen, Leo Pharma, Eli Lilly, Novartis, Pfizer and Sanofi-Genzyme. Bruno Duarte has participated in clinical trials, advisory board and/or lectures promoted by Abbvie, Almirall, Janssen, Leo Pharma, Eli Lilly, Pfizer and Sanofi-Genzyme. Maria João Paiva-Lopes has participated in clinical trials, advisory board and/or lectures promoted by AbbVie, Almirall, Boehringer Ingelheim, Janssen, Leo-Pharma, Eli Lilly, Novartis, Pfizer, Sanofi-Genzyme, Viatris. Paulo Filipe has nothing to disclose. Ethics Approval: This study did not involve new studies with human participants or animals.

Figures

Fig. 1
Fig. 1
The role of IL-4 in the four cardinal pillars of atopic dermatitis: skin barrier dysfunction, skin dysbiosis, inflammation, and pruritus
See this image and copyright information in PMC

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