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

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

doi:10.3389/fmicb.2019.02482

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

Front Microbiol. 2019 Oct 30:10:2482. doi: 10.3389/fmicb.2019.02482. eCollection 2019.

Authors

Feifei Qi^{1

2}, Mingya Liu^{1

2}, Fengdi Li^{1

2}, Qi Lv^{1

2}, Guanpeng Wang^{1

2}, Shuran Gong^{1

2}, Shunyi Wang^{1

2}, Yanfeng Xu¹, Linlin Bao^{1

2}, Chuan Qin^{1

2}

Affiliations

¹ NHC Key Laboratory of Human Disease Comparative Medicine, The Institute of Laboratory Animal Sciences, Peking Union Medical College Hospital (CAMS), Beijing, China.
² Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, The Institute of Laboratory Animal Sciences, Peking Union Medical College Hospital (CAMS), Beijing, China.

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.

Keywords: A/California/07/2009 (H1N1); Interleukin-37; inflammation; macrophages; viral pneumonia.