Rahaman, Md Mizanur, Wangchuk, Phurpa, and Sarker, Subir (2025) Targeting Interferon-Gamma (IFN-γ)-Related Signalling Pathways in Inflammatory Bowel Disease: Emerging Inhibitors and Therapeutic Advances. Mediators of Inflammation, 2025. 3181200.

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Abstract

Inflammatory bowel disease (IBD) encompasses a group of chronic and relapsing inflammatory disorders of the gastrointestinal tract, driven by a multifaceted interplay between genetic predisposition, environmental factors and dysregulated immune responses. Central to its immunopathogenesis is the aberrant activation of pro-inflammatory cytokine networks, among which interferon-gamma (IFN-γ) has been increasingly recognised as a critical mediator of mucosal damage and disease perpetuation. IFN-γ exerts pleiotropic effects on both innate and adaptive immune compartments, orchestrating a pathogenic immune milieu that disrupts intestinal epithelial integrity and sustains chronic inflammation. Recent therapeutic advances have focused on the modulation of IFN-γ signalling as a targeted approach to restoring intestinal homeostasis. A growing repertoire of IFN-γ inhibitors—including neutralising monoclonal antibodies (MAbs), small-molecule Janus kinase (JAK) inhibitors and bioactive phytochemicals—are being explored for their capacity to attenuate IFN-γ-driven inflammatory cascades. These agents offer distinct mechanistic profiles, targeting various nodes of the IFN-γ axis, and hold significant promise for addressing therapeutic gaps in refractory IBD. This review provides a comprehensive evaluation of emerging IFN-γ-targeted therapies, detailing their mechanisms of action, preclinical and clinical efficacy and translational potential. By elucidating the therapeutic landscape of IFN-γ modulation, this study aims to inform the development of more effective and personalised treatment strategies for patients with IBD.

Item ID:	89340
Item Type:	Article (Research - C1)
ISSN:	1466-1861
Keywords:	Cytokines; IBD; IFN-γ; inflammation; inhibitors
Copyright Information:	© 2025 Md. Mizanur Rahaman et al. Mediators of Inflammation published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Funders:	Australian Research Council (ARC)
Projects and Grants:	ARC DE200100367
Date Deposited:	23 Oct 2025 03:50
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320404 Cellular immunology @ 100%
SEO Codes:	20 HEALTH > 2001 Clinical health > 200102 Efficacy of medications @ 100%
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