The Role And Mechanism Of IL-37 In Severe Pneumonia Caused By H1N1 Infection

Background Influenza virus infection induces the body’s excessive immune response,promotes the secretion of cytokines in large quantities,forms a cytokine storm,and causes lung damage,lung failure and even death.At present,antiviral drugs used clinically for influenza treatment have limited therapeutic effects on suppressing severe inflammation caused by excessive immunity of the body.Interleukin-3 7(IL-37)can inhibit a variety of inflammations,prevent the occurrence of cytokine storm by inhibiting the secretion of inflammatory factors,and play an important role in infectious diseases,autoimmune diseases and tumors.Applying the anti-inflammatory effect of IL-37 to the treatment of severe pneumonia caused by H1N1 influenza virus infection will undoubtedly provide new ideas for the treatment of severe pneumonia caused by influenza.Objective Explore the role and mechanism of IL-37 in severe pneumonia caused by H1N1 infection.Methods1.IL-37 plays an anti-inflammatory effect in severe pneumonia caused by H1N1 infection1)After H1N1 infects BALB/c mice,giving IL-37 combined with Oseltamivir treatment,observing the general symptoms,weight change and survival rate of the mice;2)Different doses of IL-37 were given by nasal drops and intravenous injection at 2h,24h,and 48h after infection,and observing the general symptoms and weight changes of mice to determine the best administration conditions;2.The mechanism of IL-37’s anti-inflammatory effect in severe pneumonia caused by H1N1 infection1)Collecting mouse lung,serum,alveolar lavage fluid and other samples at different time points after infection,observing lung histopathological changes,detecting the expression level of inflammatory factors,and the changes in the proportion and type of immune cells before and after infection;2)After removing the macrophages,observing the general symptoms and weight changes of the mice;3)Using RAW264.7 to establish a cell model of H1N1 infection,and detecting its inflammatory factor mRNA and protein levels.Results1.IL-37 combined with Oseltamivir treatment significantly shortened the weight recovery time of mice and improved survival rate,confirming the therapeutic effect of IL-37 in severe pneumonia caused by H1N1 infection;2.2h after infection,intravenous injection of 12.5ug/kg of IL-37 can better reduce the weight loss rate of mice and improve their survival rate.It is clear that IL-37 is the best treatment for severe pneumonia caused by H1N1 infection.3.IL-37 combined with Oseltamivir treatment can significantly reduce the lung index of mice,the total number of inflammatory cells in the alveolar lavage fluid is reduced,the inflammatory cell infiltration in the lung is significantly improved,and the lung supernatant(MIG,RANTES,IL-10,IP-10),alveolar lavage fluid(IL-1β,MIP-1α,IFN-y,MIG,RANTES),and serum(MCP-1,IL-6)inflammatory cytokine expression levels were significantly reduced,proving that IL-37 Play an anti-inflammatory effect in severe pneumonia caused by influenza;4.After IL-37 combined with Oseltamivir treatment,the proportion of macrophages in the lung tissue of infected mice was significantly increased.After macrophages were removed,the protective effect of IL-37 combined with Oseltamivir treatment decreased,which proved that macrophages are the key immune cells for severe pneumonia caused by virus infection in the process of IL-37 functioning;5.MAPK signaling pathway proteins(P38,ERK,NLRP3)are the key signaling molecules for IL-37 to play an anti-inflammatory effect in severe pneumonia caused by H1N1 infection.Conclusions IL-37 reduces the expression of inflammatory cytokines through the MAPK signaling pathway,and plays an anti-inflammatory effect in severe pneumonia caused by H1N1 infection.