Open Access
REVIEW
Therapeutic effects of IFN-gamma on chronic conditions in Mustard Lung disease: a scoping systematic review
Fatemeh Rafiei1, Ahmad Chitsaz-Sadeghi1, Mohammad Alizadeh1, Jafar Salimian2, Sadegh Azimzadeh-Jamalkandi1,*, Mostafa Ghanei1
1 Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
2 Applied Virology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
* Corresponding Author: Sadegh Azimzadeh-Jamalkandi. Email: 
, 
European Cytokine Network https://doi.org/10.32604/ecn.2026.077328
Received 07 December 2025; Accepted 09 May 2026; Published online 29 June 2026
Abstract
Objectives: Mustard Lung disease, a chronic respiratory condition caused by sulfur mustard exposure, involves dysregulated inflammation and repair. This scoping systematic review aims to investigate interferon-gamma (IFN-γ) as a potential therapeutic agent, leveraging its anti-inflammatory and tissue-healing properties. Methods: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a structured search (through July 2025) across major databases (Scopus, Web of Science, PubMed, Google Scholar, Scientific Information Database) utilized “sulfur mustard” and “interferon-gamma” keywords. Studies reporting cellular and molecular data in humans or animals were screened. Extracted findings were integrated to construct a comprehensive knowledge-based IFN-γ signaling pathway, extended to incorporate sulfur mustard injury mechanisms, with expression changes visually mapped. Results: Based on the systematic review, 19 chronic SM studies were included: 9 human (2 clinical trials) and 10 animal studies. Both IFN-γ clinical trials showed improved symptoms, lung function (FEV1, FVC), quality of life (SGRQ, CAT), and reduced inflammatory cytokines (TGF-β, TNF-α). This effect is hypothesized via an immune shift from pro-fibrotic Th2/Th17 to a Th1 type. Observational human studies showed inconsistent baseline IFN-γ serum levels. Animal studies measured IFN-γ alterations but did not evaluate therapeutic administration. Mild influenza-like side effects occurred in one trial. Conclusions: IFN-γ is a promising therapeutic for Mustard Lung disease, improving symptoms and function, likely by shifting the immune response from a pro-fibrotic Th2/Th17 to a protective Th1 type. However, limitations exist (small, heterogeneous studies; side effects), requiring further research on signaling balance (TGF-β/IFN-γ), combination therapies, and precise patient categorization.
Keywords
Airway remodeling; bronchitis; combination therapies; interferon-gamma; Mustard Lung disease; tissue remodeling
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