REVIEW: Role of Cytokines IL-25, IL-33, and TSLP in the Respiratory Tract Inflammation: Therapeutic Perspectives

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Ekaterina D. Timotievich^1,a*, Igor P. Shilovskiy¹, Danila A. Gurskii¹, Anatoli D. Taganovich², Aleksei G. Kadushkin², and Musa R. Khaitov^1,3

¹Federal State Budgetary Institution “National Research Center – Institute of Immunology”, Federal Medical-Biological Agency, 115522 Moscow, Russia

²Belarusian State Medical University, Minsk, 220083, Republic of Belarus

³N. I. Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, 117997 Moscow, Russia

^* To whom correspondence should be addressed.

Received: August 17, 2025; Revised: October 16, 2025; Accepted: November 4, 2025

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In recent years, understanding of the key role of epithelial cytokines (IL-25, IL-33, and TSLP) in the development of respiratory tract inflammatory diseases has significantly expanded. These molecules, released by airway epithelium in response to allergens, pathogens, and damaging agents, act as alarmins, initiating a cascade of the Th2-mediated inflammation that leads to the IgE-mediated reactions, eosinophilic infiltration, and tissue remodeling. Beyond classical allergic processes, epithelial cytokines play a crucial role in the virus-induced exacerbations of respiratory diseases and pathogenesis of chronic obstructive pulmonary disease (COPD). Monoclonal antibody therapeutics targeting these cytokines have demonstrated efficacy in treating severe asthma. This review summarizes current data on contribution of TSLP, IL-33, and IL-25 to the respiratory tract inflammation and discusses the prospects of their targeted inhibition to improve therapeutic efficacy.

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KEY WORDS: epithelial cytokines, interleukin-25, interleukin-33, thymic stromal lymphopoietin, inflammation, allergy, bronchial asthma, COPD, targeted therapy

DOI: 10.1134/S0006297925602655

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