Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 05 06 1 10 EN Amirhossein Faghih Ojaroodi Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran AND Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran Neda Gholamzadeh Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences, Tabriz, Iran AND Department of Internal Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Khadijeh Pouya Department of Gynecology and Obstetrics, Faculty of Medicine, Tabriz Medical Sciences Islamic Azad University, Tabriz, Iran Sanaz Abbaspour-Aghdam Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Haleh Mikaeili Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences, Tabriz, Iran AND Department of Internal Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Armin Sadeghi Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences, Tabriz, Iran AND Department of Internal Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Majid Ahmadi Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Mehdi Nadiri Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences, Tabriz, Iran AND Department of Internal Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran 2025 10 21 2026 01 31 Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory lung condition and a leading cause of morbidity and mortality worldwide. Despite well-established links to smoking, emerging evidence highlights the involvement of complex immune and epigenetic mechanisms in its pathogenesis. This study aimed to investigate the expression, secretion, and promoter methylation status of key pro- and anti-inflammatory cytokines in peripheral blood mononuclear cells (PBMCs) of patients with mild and severe COPD, compared with healthy individuals. PBMCs were isolated from 90 participants divided into three groups: severe COPD, mild COPD, and healthy controls. Quantitative polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and methylation-specific PCR were employed to evaluate gene expression, protein secretion, and promoter methylation of inflammatory cytokines. Patients with COPD exhibited significant upregulation of pro-inflammatory cytokines (Interleukin1β (IL-1β), IL-6, IL-18, IFN-γ, and TNF-α) at both transcript and protein levels, with more pronounced alterations in the severe group. Conversely, anti-inflammatory mediators (IL-10 and TGF-β) were significantly downregulated. Promoter methylation analysis revealed hypomethylation in pro-inflammatory cytokine genes and hypermethylation in anti-inflammatory ones, correlating with disease severity. The findings demonstrate that COPD progression is associated with a shift toward a hyper-inflammatory, hypo-regulatory immune phenotype sustained by epigenetic modifications. These results support the potential for integrating cytokine-methylation signatures into clinical staging and for targeting epigenetic and immune pathways in future therapeutic strategies. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4638 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4638/2336