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IL-37 possesses both anti-inflammatory and antiviral effects against Middle East respiratory syndrome coronavirus infection

摘要Background:The aim was to elucidate the function of IL-37 in middle east respiratory syndrome coronavirus(MERS-CoV)infection,thereby providing a novel therapeutic strategy for managing the clinical treatment of inflammatory response caused by res-piratory virus infection.Methods:We investigated the development of MERS by infecting hDPP4 mice with hCoV-EMC(107 TCID50[50%tissue culture infectious dose])intranasally.We in-fected A549 cells with MERS-CoV,which concurrently interfered with IL-37,detect-ing the viral titer,viral load,and cytokine expression at certain points postinfection.Meanwhile,we administered IL-37(12.5μg/kg)intravenously to hDPP4 mice 2 h after MERS-CoV-2 infection and collected the serum and lungs 5days after infection to investigate the efficacy of IL-37 in MERS-CoV infection.Results:The viral titer of MERS-CoV-infected A549 cells interfering with IL-37 was significantly reduced by 4.7-fold,and the viral load of MERS-CoV-infected hDPP4 mice was decreased by 59-fold in lung tissue.Furthermore,the administration of IL-37 suppressed inflammatory cytokine and chemokine(monocyte chemoattractant pro-tein 1,interferon-y,and IL-17A)expression and ameliorated the infiltration of inflam-matory cells in hDPP4 mice.Conclusion:IL-37 exhibits protective properties in severe pneumonia induced by MERS-CoV infection.This effect is achieved through attenuation of lung viral load,suppression of inflammatory cytokine secretion,reduction in inflammatory cell infil-tration,and mitigation of pulmonary injury.

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