Related Experiment Video
Updated: May 28, 2025
Imaging Cell Interaction in Tracheal Mucosa During Influenza Virus Infection Using Two-photon Intravital Microscopy
Published on: August 17, 2018
Interleukin-35 mRNA therapy for influenza virus-induced pneumonia in mice
Yanyan Li1, Yuqin Liao2, Yiqi Miao2
1Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, 421001, PR China; Bioinformatics Center of AMMS, Beijing, 100850, PR China.
Abstract:
Influenza virus-induced pneumonia is a common complication caused by influenza A virus infection and causes severe lung inflammation. After infection, the body induces an active immune response that can produce cytokine storm, leading to increased expression of pro-inflammatory factors and tissue damage. Interleukin-35 (IL-35) is a recently identified cytokine associated with viral infection. IL-35 may inhibit the inflammation caused by viral infection and therefore may be developed into an antiviral treatment. Compared with traditional drugs, mRNA drugs have the advantages of simple production process, short development cycle, strong target specificity, high safety, and long-lasting action. In this study,we prepared IL-35 mRNA and IL-35 mRNA/Lipid Nanoparticle (IL-35 mRNA/LNP). To investigate the role of IL-35 mRNA in the host defense against post-influenza pneumonia, a mouse model of pneumonia caused by influenza infection was established. After influenza infection, the mice produced a large number of inflammatory factors that caused lung tissue damage, while administration of IL-35 mRNA/LNP effectively reduced the inflammatory response and improved the survival rate of mice. In addition, mice injected with IL-35 mRNA/LNP (125 μg/kg) directly via tail vein did not show significant inflammatory responses or tissue damage. These data suggest that IL-35 mRNA attenuates the inflammatory response caused by influenza virus infection and shows potential for development as a new drug for the treatment of influenza virus-induced pneumonia.
Insights
Interleukin-35 (IL-35) mRNA delivered via lipid nanoparticles effectively reduced lung inflammation and improved survival in a mouse model of influenza virus-induced pneumonia, showing potential as an antiviral therapy.
Area of Science:
- Immunology
- Virology
- Nanomedicine
Background:
- Influenza A virus infection can cause severe pneumonia and lung inflammation.
- Cytokine storm, driven by pro-inflammatory factors, exacerbates tissue damage during influenza.
- Interleukin-35 (IL-35) is a novel cytokine with potential anti-inflammatory properties relevant to viral infections.
Purpose of the Study:
- To investigate the therapeutic potential of IL-35 mRNA delivered via lipid nanoparticles (LNPs) for influenza virus-induced pneumonia.
- To evaluate the efficacy of IL-35 mRNA/LNP in mitigating lung inflammation and improving host defense against influenza.
Main Methods:
- Preparation of IL-35 mRNA and IL-35 mRNA/LNP formulations.
- Establishment of a mouse model of pneumonia following influenza virus infection.
- Administration of IL-35 mRNA/LNP to infected mice and assessment of inflammatory responses and survival rates.
Main Results:
- Influenza infection induced significant inflammatory responses and lung tissue damage in mice.
- Treatment with IL-35 mRNA/LNP effectively reduced the inflammatory response in the lungs.
- IL-35 mRNA/LNP administration improved the survival rate of mice with influenza-induced pneumonia.
- Direct tail vein injection of IL-35 mRNA/LNP did not cause significant adverse inflammatory effects or tissue damage.
Conclusions:
- IL-35 mRNA, delivered via LNPs, demonstrates potent anti-inflammatory effects against influenza virus-induced pneumonia.
- IL-35 mRNA/LNP represents a promising therapeutic strategy for treating influenza-related lung complications.
- This approach highlights the potential of mRNA therapeutics in managing viral respiratory infections.
