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IL-37 possesses both anti-inflammatory and antiviral effects against Middle East respiratory syndrome coronavirus
Feifei Qi1,2, Yiwei Yan1, Qi Lv1,2
1Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, NHC Key Laboratory of Comparative Medicine, Institute of Laboratory Animal Science, CAMS & PUMC, Beijing, China.
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 respiratory 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 infected A549 cells with MERS-CoV, which concurrently interfered with IL-37, detecting the viral titer, viral load, and cytokine expression at certain points postinfection. Meanwhile, we administered IL-37 (12.5 μg/kg) intravenously to hDPP4 mice 2 h after MERS-CoV-2 infection and collected the serum and lungs 5 days 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 protein 1, interferon-γ, and IL-17A) expression and ameliorated the infiltration of inflammatory 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 infiltration, and mitigation of pulmonary injury.
Insights
Interleukin-37 (IL-37) significantly reduces Middle East respiratory syndrome coronavirus (MERS-CoV) viral load and suppresses inflammation. This finding offers a potential therapeutic strategy for MERS-CoV-induced pneumonia.
Area of Science:
- Virology
- Immunology
- Respiratory Medicine
Background:
- Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes significant inflammatory responses.
- Understanding the role of IL-37 in MERS-CoV infection is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To investigate the function of Interleukin-37 (IL-37) in MERS-CoV infection.
- To explore IL-37 as a potential therapeutic agent for MERS-CoV-induced inflammatory conditions.
Main Methods:
- MERS-CoV infection model in hDPP4 mice and A549 cells.
- Interference with IL-37 and subsequent measurement of viral titer and load.
- Intravenous administration of IL-37 to infected mice to assess therapeutic efficacy.
Main Results:
- IL-37 interference significantly reduced MERS-CoV viral titer in A549 cells (4.7-fold).
- IL-37 administration decreased MERS-CoV viral load in mouse lung tissue (59-fold).
- IL-37 suppressed key inflammatory cytokines (MCP-1, IFN-γ, IL-17A) and reduced inflammatory cell infiltration.
Conclusions:
- IL-37 demonstrates protective effects against severe pneumonia caused by MERS-CoV.
- IL-37 attenuates viral load, suppresses inflammation, and mitigates lung injury in MERS-CoV infection.
- IL-37 represents a promising therapeutic target for managing MERS-CoV-related respiratory illness.
