Interleukin-37 Ameliorates Influenza Pneumonia by Attenuating Macrophage Cytokine Production in a MAPK-Dependent Manner

Feifei Qi; Feifei Qi; Mingya Liu; Mingya Liu; Fengdi Li; Fengdi Li; Qi Lv; Qi Lv; Guanpeng Wang; Guanpeng Wang; Shuran Gong; Shuran Gong; Shunyi Wang; Shunyi Wang; Yanfeng Xu; Linlin Bao; Linlin Bao; Chuan Qin; Chuan Qin

Interleukin-37 Ameliorates Influenza Pneumonia by Attenuating Macrophage Cytokine Production in a MAPK-Dependent Manner

2019

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.

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