Profiles and Predictive Value of Cytokines in Children with Human Metapneumovirus Pneumonia

Abstract

Background: Human metapneumovirus (HMPV) is an important cause of respiratory tract infections in young children. To evaluate the predicitive value of Th1/Th2 cytokines which include IL-2, IL-4, IL-6, IL-10, INF-γ and TNF-α in pneumonia caused by HMPV. Methods: A retrospective study was performed among 59 pneumonia pediatric patients with HMPV infection and 33 healthy children as the control cohort, which was detected by the immunofluorescence assay, and the Th1/Th2 cytokines were measured by flow cytometry. Results: When compared with the healthy children, children who were infected with HMPV pneumonia had a significantly lower level of IL-2 (p<0.001) and higher levels of IL-4 ((p<0.001), IL-6 (p=0.001), IL-10 (p<0.001), and IFN-γ (p<0.001). Compared with patients diagnosed with influenza virus A (IVA) or influenza virus B (IVB) infections, HMPV-positive patients had significantly higher levels of IL-4 (p<0.001 and <0.001), IFN-γ (p<0.001 and <0.001), and TNF-α (p<0.001 and 0.016). Moreover, compared with IVA patients, HMPV-positive patients had a significantly lower level of IL-6 (p=0.033). Finally, when comparing cytokine levels among the patients with HMPV pneumonia, IL-6 and TNF-α levels were found to be significantly higher in the severe group than the mild group (p=0.027 and 0.049). The IL-6 and TNF-α were used to differentiate between mild and severe symptoms in children diagnosed with HMPV pneumonia with an AUC of 0.678 (95% CI, 0.526-0.829) and 0.658 (95% CI, 0.506-0.809), respectively.Conclusions: Our study indicates that IL-2, IL-4, IL-6, IL-10, and IFN-γ may be a reference for auxiliary diagnose HMPV pneumonia in children. IL-4, TNF-α, and IFN-γ may serve as biomarkers to distinguish HMPV from IVA and IVB, whereas IL-6 may be able to differentiate between HMPV and IVA. IL-6 and TNF-α may be used to assessment of severity and prognosis of HMPV infection.