The Therapeutic Effect Of IL-4 On Acute Lung Injury Induced By Endotoxin In Mice

Objective: Acute lung injury(ALI)is a common clinically critical disease.Severe ALI is easily developed into acute respiratory ditress syndrome(ARDS),characteristic by progressive respiratory distress and refractory hypoxemia.Due to the lack of effective treatment methods,the mortality rate of the ALI is as high as 30-40%,which causes serious harm to the health of the people.The essence of ALI is the uncontrolled inflammatory response in the body,among them,the imbalance of pro-inflammatory and anti-inflammatory factors is the key to the uncontrolled inflammatory response.Therefore,reconstruction of the balance between pro-inflammatory and antiinflammatory factors is expected to become a new strategy for the treatment of ALI.Interleukin-4(IL-4),an immunologically active cytokine which is mainly produced by Th2 cells,can inhibit the secretion of pro-inflammatory cytokines such as IL-1?,IL-6,tumor necrosis factor-?(TNF-?).Meanwhile,IL-4 promotes the secretion of antiinflammatory cytokines such as IL-10,IL-13.Thus,which is beneficial to restore the balance between pro-inflammatory and anti-inflammatory factors,and may become an ideal drug for the treatment of ALI.Therefore,this study was designed to evaluate the therapeutic effect of IL-4 on ALI in C57BL/6J mice.Methods: Female,healthy C57BL/6J mice were randomly divided into 3 groups: control group,LPS group and IL-4 group.Firstly,mice in LPS group and IL-4 group were treated with LPS(15 mg/kg)by trachea,and equal volume of PBS was given to the control group mice.Then,after 0.5 h,IL-4(10 ?g/kg)was intratracheally instilled into the IL-4 group,while an equal volume of PBS was instilled into the the LPS group and control group mice.In addition,the general state,such as mental state,eating status,and reaction ability of mice in different groups was observed.Finally,lung samples were collected at 6 h and 48 h after LPS administered for further analysis.The lungs were stained with Hematoxylin-eosin(HE)to evaluate the degree of pathological damage in mice,and determine the wet-to-dry weight ratio of lung tissue in mice.The total protein in bronchoalveolar lavage fluid(BALF)was determined by BCA protein assay,and the secretion of inflammatory factors such as TNF-?,IL-1? and IL-6 was determined by ELISA and mRNA expression in mouse lung homogenate were determined by q-PCR.Results:(1)Compared with the control group,the lung tissue of LPS group showed pathological changes such as alveolar wall thickening,alveolar structure destruction and inflammatory cell infiltration,and the protein content exuded in the BALF significantly increased.Meanwhile,the secretion of TNF-?,IL-6 and IL-1? was also significantly increased,which indicating the ALI mice model was successfully constructed.(2)At 6 h after LPS administered,compared with LPS group,the general condition of the mice in IL-4 group was improved,and the lung tissue injury score was significantly decreased(P < 0.01).The total protein in BALF was significantly decreased(P < 0.01),and the secretion of IL-1? and IL-6 in the lung homogenate was also significantly decreased(P < 0.01)in IL-4 group.The wet-to-dry weight ratio of lung tissue and the relative mRNA expression of tnf-?,Il-6,Il-1b was decreased,but there was no significantly differences.(3)At 48 h after LPS administered,compared with LPS group mice,the pathological injury score of lung tissue,the wet-to-dry weight ratio of lung tissue,the total protein in BALF and the secretion of TNF-?,IL-6,IL-1? were all decreased in the IL-4 group,however,there was no significantly differences.Conclusion:(1)ALI model could be established after intratracheal instillation of LPS;(2)Exogenous IL-4 had a significant therapeutic effect on LPS-induced ALI in mice for 6 h,but the therapeutic effect weakened as the treatment time extended to 48 h;(3)The therapeutic effect of IL-4 on ALI mice model might be related to its inhibition of the secretion of pro-inflammatory factors,such as IL-6 and IL-1? in lung tissue.