Interleukin 16 and 25 (IL-17E) and Clinical Outcomes in Exacerbation of COPD—A Pilot Study

<b>Background:</b> Exacerbation of chronic obstructive pulmonary disease (ECOPD) significantly impact health status, hospitalization rates, and disease progression, and are linked to increased mortality. Predictive factors for ECOPD are therefore of considerable interest. The limited understanding of interleukin 16 (IL-16) and IL-25 role in ECOPD provided the rationale for this study. <b>Methods</b>: Fifty ex-smokers diagnosed with COPD (22 ECOPD and 28 patients in the stable phase of the disease) underwent prospective analysis to evaluate the role of I IL-25 as predictive markers of clinical outcomes in ECOPD. <b>Results:</b> We observed a significantly lower IL-16 and higher IL-25 concentrations among ECOPD patients (<i>p</i> = 0.002 and <i>p</i> = 0.01 respectively). We also detected a significant negative correlation between IL-16 and neutrophil-to-lymphocyte ratio (NLR) (<i>p</i> = 0.04) and a significant negative correlation between IL-25 concentration and absolute eosinophil count (<i>p</i> = 0.04). In the entire group, we observed a positive correlation between IL-16 and both FEV1 and FVC, both expressed as a percentage of reference value, (<i>p</i> = 0.002 and <i>p</i> = 0.0004 respectively). However, after stratification to ECOPD and stable COPD group, significance maintained for FVC (<i>p</i> = 0.045 for ECOPD and <i>p</i> = 0.02 for stable COPD). In survival analysis, we detected significantly lower all-cause mortality for 3rd tertile of IL-16 concentrations, with a hazard ratio of 0.33 (95%CI: 0.11-0.98; <i>p</i> = 0.04). <b>Conclusions</b>: Lower IL-16 levels among ECOPD patients may indicate a feedback mechanism linked to heightened Th1 response activation. Observed correlations with ventilatory parameters and survival also seems to reflect this mechanism. The higher IL-25 concentrations observed in ECOPD patients, along with the negative correlation with absolute eosinophil count and eosinopenia, suggest multifactorial regulation and independent functions of eosinophils and IL-25. Hypothetically, this paradox may be related to the Th1/Th2 imbalance favoring Th1 response. Obtained results should be reproduced in larger size samples.