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Interleukin (IL)-41 is a novel immunomodulatory cytokine involved in the pathogenesis of several inflammatory and metabolic illnesses. However, it remains unclear how IL-41 contributes to the pathogenesis of chronic obstructive pulmonary disease (COPD). Therefore, the aim of the present study was to explore the correlation between the expression level of IL-41 and acute exacerbation of COPD (AECOPD). In total, 107 patients with COPD and 56 healthy controls were recruited from the First Affiliated Hospital of Ningbo University (Ningbo, China). Serum IL-41, IL-6, and matrix metalloproteinase-2 (MMP-2) levels were evaluated using enzyme-linked immunosorbent assay. Serum amyloid A (SAA) and C-reactive protein (CRP) levels were assessed in the hospital laboratory. The levels of IL-41 were higher in the AECOPD group than in the stable COPD (SCOPD) and control groups (P<0.0001). IL-6, SAA and CRP levels, the percentage of neutrophils, as well as neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios were higher in the AECOPD group than those in the SCOPD and control groups. The smoking index was positively correlated with serum IL-41, CRP and SAA levels. The expression level of IL-41 was correlated with the number of acute exacerbations, severity of the exacerbations, and COPD assessment test scores in the AECOPD group. Examination of the receiver operating characteristic (ROC) curves showed that IL-41, especially when combined with other inflammatory factors, had a specific diagnostic value for AECOPD. According to the ROC curve analysis, the area under the curve (AUC) for IL-41 was 0.742 (P=0.051), and the AUC for IL-41 combined with other inflammatory factors was 0.925 (P=0.030). Increased serum IL-41 levels were associated with AECOPD and may play a role in the monitoring and evaluation of COPD. [ABSTRACT FROM AUTHOR]