Role And Mechanism Of Glucocorticoid And Complement Inhibitors In The Treatment Of Severe Pneumonia Caused By Influenza Virus

Influenza virus infection can cause viral pneumonia and acute lung injury.In severe cases,severe pneumonia may develop and cause acute respiratory distress syndrome.The main manifestations are ventilation obstruction,rapid and large number of inflammatory cell infiltration of lung tissue,septic shock and acute renal failure,which are characterized by high incidence and mortality.In recent years,the spread of H5N1,H7N9 and other avian influenza has posed a great threat to global public health security and aroused worldwide attention.In recent years,it has been proved that the cause of systemic inflammation in patients with severe pneumonia is not only the infection of virus,but also the excessive activation of innate immune system in the body,triggering inflammatory cytokine storm and causing immune damage.Previous studies have shown that complement system plays an important role in the process of innate immune response,and the imbalance of complement system will lead to excessive inflammatory response in the body,which can trigger "cytokine storm" and cause tissue immune pathological damage.Currently,there is no specific and effective intervention method for the treatment of severe pneumonia caused by influenza.Glucocorticoid shock therapy or combination of low-dose glucocorticoids and antiviral drugs are often used,but the therapeutic effect is often unclear.There is no clear and uniform standard for the specific use of glucocorticoids in clinical practice.At present,there is a great controversy on the use of glucocorticoid intervention in the treatment of severe pneumonia caused by influenza virus infection at home and abroad.At the same time,for the intervention of severe pneumonia,domestic and foreign countries have been constantly exploring and discovering new methods of treatment through intervention of excessive immune and inflammatory response.In this study,the effects of glucocorticoids and complement inhibitors on severe pneumonia caused by influenza virus were systematically studied.ObjectiveThis study aims to explore the effects of different doses and methods of glucocorticoid therapy on severe pneumonia,compare the effect and mechanism of glucocorticoid and complement inhibitor on severe pneumonia based on the model of severe pneumonia caused by influenza virus infection,to provides theoretical basis for rational use of glucocorticoids and exploration of new treatment methods for severe pneumonia.Methods1.To study the therapeutic effect of different glucocorticoid therapy in mice with different severity of pneumonia.Different doses of glucocorticoids were used to treat the mice with different severity of pneumonia at different time points.The status ofthe mice was observed,the vital signs and death changes of the mice were recorded,and the levels of inflammatory cytokines and chemokines in the plasma of the mice were analyzed by liquid chip analysis.2.To compare the effects of glucocorticoid and complement regulation on severe pneumonia caused by PR8 virus infection,Mice with severe pneumonia caused by PR8 virus were treated with complement inhibitors and different doses of glucocorticoids.observed the survival state of the mouse,and clinical signs,HE dyeing observation lung tissue pathological injury in mice,immunohistochemical(IHC)to detect virus antigen in the expression and distribution of lung tissue in mice,mice liquid chip technology to detect the levels of plasma inflammatory cytokines and chemokines in the,flow cytometry to detect the CD4 / CD8 ratio in the mice alveolar lavage fluid,virus plaque experimental determination of the lung tissue of mice viral load.Result1.A severe pneumonia mouse model was established by infecting BALB/c mice with PR8 influenza virus.The results showed that the clinical signs such as trichotilloma and decreased mobility were earlier and more serious in mice treated with high and low doses of glucocorticoids than in untreated control mice.Mice treated with high-dose glucocorticoids breathed more rapidly,lost weight the fastest and died the fastest,followed by those treated with low-dose glucocorticoids.The results showed that the treatment of severe pneumonia caused by influenza virus with glucocorticoids could not achieve significant therapeutic effect,and the use of high-dose glucocorticoids accelerated the death of mice.2.By comparing the effects of glucocorticoid and complement regulation on the treatment of severe pneumonia caused by PR8 virus infection,it was found that the weight loss was the fastest in the high-dose group and the control group,followed by the low-dose group,and the weight loss was the slowest in the antibody treatment group.The proportion of CD4/CD8 in antibody treatment group was significantly higher than that in other groups.The levels of inflammatory cytokines ip-10 and KC in peripheral blood of mice were higher in the high-dose glucocorticoid group than in the low-dose glucocorticoid group and complement blocker group,and the infiltration of inflammatory cells in lung tissues was also significantly higher than in other groups.The results of plaque assay showed that the lung viral load of mice in the high-dose glucocorticoid therapy group was higher than that in other groups,and thelung tissue with positive viral antigen was the most widely distributed in the lung tissue of mice in the high-dose glucocorticoid therapy group.The results showed that complement inhibitors could improve the survival of mice with severe pneumonia caused by influenza virus,and significantly reduce the body inflammation and lung tissue pathological damage caused by virus infection.ConclusionTreatment of severe pneumonia caused by influenza virus infection with high dose of glucocorticoids is not effective,and has side effects.It may be an effective intervention method to treat severe pneumonia caused by influenza virus infection by inhibiting or blocking the over-activation of complement and reducing inflammatory injury.