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. Early innate immune response to HMPV is focused on induction of antiviral interferons (IFNs) and other pro-inflammatory cytokines that are critical for the formation of adaptive immune responses. To evaluate the predictive 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. 131 children infected with Influenza virus A (IVA) and 41 children infected with influenza virus B (IVB) were detected by RT-PCR assay in throat swabs. 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 IVA or IVB infection, 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 symptoms 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. Conclusion: Our study indicated that difference in cytokine trends depending on the virus species. The levels of IL-4, TNF-α and IFN-γ were significantly distinguished in children infected with HMPV versus IVA and IVB. IL-6 and TNF-α may be helpful in assessing the severity and prognosis of HMPV infection.