Cytokines and COPD: The Next Frontier in Biologic Therapy

Abstract

Chronic obstructive pulmonary disease (COPD) is a heterogeneous respiratory disorder characterized by persistent airway inflammation, progressive airflow limitation, and recurrent exacerbations. Recent advances in immunology have highlighted the role of distinct cytokine-mediated pathways in driving COPD pathogenesis, including Type 2 (T2) inflammation, Th17-associated responses, and neutrophilic immune activation. Targeted biologic therapies, such as anti–IL-5, IL-13, IL-33, IL-22, IL-36, IL-17, TRAIL, and TSLP blockers, are emerging as potential precision medicine strategies aimed at modulating specific inflammatory endotypes. Anti–IL-5 antibodies reduce eosinophil-driven inflammation, whereas IL-13 and IL-33 inhibitors disrupt upstream T2 cytokine signaling. IL-22 and IL-36 blockade targets tissue inflammation and neutrophilic responses, and IL-17A/C inhibition addresses chronic airway neutrophilia and exacerbation risk. TRAIL and TSLP blockers offer novel approaches to limit epithelial damage and upstream T2 immune activation. While clinical trials show promising results in selected patient populations, therapeutic efficacy is closely linked to biomarker-driven patient stratification, and long-term safety remains under investigation. Collectively, these targeted interventions represent a shift toward endotype-specific management in COPD, offering opportunities to improve outcomes for patients with refractory inflammation and frequent exacerbations