Abstract
Viral pneumonitis caused by influenza A (H1N1) virus leads to high levels of morbidity and mortality. Given the limited treatment options for severe influenza pneumonia, it is necessary to explore effective amelioration approaches. Interleukin-37 (IL-37) has been reported to inhibit excessive immune responses and protect against a variety of inflammatory diseases. In this study, by using BALB/c mice intranasally infected with A/California/07/2009 (H1N1), we found that IL-37 treatment increases the survival rate and body weight, and reduces the pulmonary index, impaired the lung injury and decreased production of pro-inflammatory cytokines in the BALF and lung tissue. Moreover, IL-37 administration enhanced not only the percentage of macrophages, but also the percentage of IL-18Rα+ macrophages, suggesting that enhancing the macrophages function may improve outcomes in a murine model of H1N1 infection. Indeed, macrophages depletion reduced the protective effect of IL-37 during H1N1 infection. Furthermore, IL-37 administration inhibited MAPK signaling in RAW264.7 cells infected with H1N1. This study demonstrates that IL-37 treatment can ameliorate influenza pneumonia by attenuating cytokine production, especially by macrophages. Thus, IL-37 might serve as a promising new target for the treatment of influenza A-induced pneumonia.
Highlights
In uenza H1N1 infection induced “ u”-like illness or pneumonia depends on the infecting strain, host immune system, and environmental factors (Rice et al, 2012; Daoud et al, 2019)
Little is known about the function of IL-37 in the in uenza-infected murine model, the regulatory role in viral pneumonia induced by A/ California/07/2009 (H1N1) infection. us, in the present study, we focused on IL-37 treatment in H1N1-infected mice, to investigate the therapeutic e ect and the mechanisms by which IL-37 treatment ameliorates in uenza pneumonia
To explore the e cacy of the recombinant IL-37 protein, BALB/c mice challenged intranasally with 50 μl H1N1 were treated with oseltamivir phosphate for 5 days with/without recombinant IL-37 for 7 days at 2 h.p.i
Summary
In uenza H1N1 infection induced “ u”-like illness or pneumonia depends on the infecting strain, host immune system, and environmental factors (Rice et al, 2012; Daoud et al, 2019). Increasing evidence has demonstrated that it is an excessively activated immune response, not a direct viral infection that leads to the increasing in uenza pneumonia severity (Morita et al, 2013; Uematsu et al, 2015). IL-37 has been shown to increase the survival rate and body weight, and downregulated the production of IL-6 and IL-17A in a coxsackievirus B3-induced model of murine viral myocarditis (An et al, 2017). Increasing evidence suggests that IL-37 can inhibit excessive immune responses and protect against a variety of in ammatory diseases, autoimmune diseases, and tumors. Little is known about the function of IL-37 in the in uenza-infected murine model, the regulatory role in viral pneumonia induced by A/ California/07/2009 (H1N1) infection. Little is known about the function of IL-37 in the in uenza-infected murine model, the regulatory role in viral pneumonia induced by A/ California/07/2009 (H1N1) infection. us, in the present study, we focused on IL-37 treatment in H1N1-infected mice, to investigate the therapeutic e ect and the mechanisms by which IL-37 treatment ameliorates in uenza pneumonia
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call