IL-4 and IL-13 in Cardiovascular Disease: From Immune Modulation to Therapeutic Possibilities – A Narrative Review

Ahmet Turhan Kılıç,1 Rıdvan Bora,2 Burak Toprak1 1Department of Cardiovascular Surgery, Mersin City Education and Research Hospital, Mersin, Turkey; 2Department of Cardiology, Tarsus State Hospital, Mersin, TurkeyCorrespondence: Burak Toprak, Department of Cardiovascular Surgery, Mersin City Education and Research Hospital, Kuzeykent District, 31131 Street No: 1, Floor: 6, Flat No: 11, Yenişehir, Mersin, 33120, Turkey, Email [email protected]: Interleukin-4 (IL-4) and Interleukin-13 (IL-13) are central regulators of the Th2 immune response and play pivotal roles in vascular inflammation, endothelial dysfunction, and cardiovascular remodeling. While their contributions to immune modulation are well known, their precise effects on the cardiovascular system remain an evolving field of study.Aim: This review aims to explore the mechanistic roles of IL-4 and IL-13 in endothelial dysfunction and the development of cardiovascular diseases, and to evaluate the therapeutic potential and risks associated with IL-4/IL-13 inhibitors.Methods: A narrative review approach was used. Articles published between 2015 and 2025 were identified through PubMed, Scopus, and Google Scholar using relevant keywords. Mechanistic, experimental, and clinical studies examining IL-4/IL-13 signaling and inhibitor outcomes were selected.Results: IL-4 and IL-13 contribute to vascular inflammation by upregulating adhesion molecules, disrupting nitric oxide synthesis via arginase I, and increasing oxidative stress. These cytokines promote vascular remodeling and are linked to hypertension, atherosclerosis, and cardiac fibrosis. Inhibitors like dupilumab show promise in controlling inflammation, but their long-term cardiovascular effects remain unclear. Some studies suggest potential risks such as increased infections, metabolic dysregulation, and vascular stiffening.Conclusion: IL-4 and IL-13 are active mediators in cardiovascular pathology, offering both therapeutic potential and clinical challenges. While inhibitors targeting these cytokines may reduce inflammation, their broader impacts on vascular health warrant cautious and personalized application until long-term cardiovascular outcomes are clarified through further research.Keywords: IL-4, IL-13, endothelial dysfunction, cardiovascular disease, cytokine inhibition