Specific Cytokine Profiles Predict the Severity of Influenza A Pneumonia: A Prospectively Multicenter Pilot Study

Abstract

Purpose. Studying the cytokine profiles in influenza A pneumonia could be helpful to better understand the pathogenesis of the disease and predict its prognosis. Patients and Methods. Patients with influenza A pneumonia (including 2009H1N1, H1N1, H3N1, and H7N1) hospitalized in six hospitals from January 2017 to October 2018 were enrolled (ClinicalTrials.gov ID, NCT03093220). Sputum samples were collected within 24 hours after admission and subsequently analyzed for cytokine profiles using a Luminex assay. Results. A total of 35 patients with influenza A pneumonia were included in the study. The levels of IL-6, IFN-γ, and IL-2 were increased in patients with severe influenza A pneumonia (n =10) ( $P=0.002$ , 0.009, and 0.008, respectively), while those of IL-5, IL-25, IL-17A, and IL-22 were decreased compared to patients with nonsevere pneumonia ( $P=0.0001$ , 0.009, 0.0001, and 0.006, respectively). The levels of IL-2 and IL-6 in the nonsurvivors ( $n=5$ ) were significantly higher than those in the survivors ( $P=0.043$ and 0.0001, respectively), while the levels of IL-5, IL-17A, and IL-22 were significantly lower ( $P=0.001$ , 0.012, and 0.043, respectively). The IL-4/IL-17A ratio has the potential to be a good predictor ( $\text{AUC}=0.94$ , $P<0.05$ , $\text{sensitivity}=88.89\%$ , $\text{specificity}=92.31\%$ ) and an independent risk factor (OR, 95% CI: 3.772, 1.188-11.975; $P<0.05$ ) for intermittent positive pressure ventilation (n = 9). Conclusion. Significant dysregulation of cytokine profiles can be observed in patients with severe influenza A pneumonia.