Interleukin-35 mRNA therapy for influenza virus-induced pneumonia in mice

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.