Changes And Significance Of IL-6 And TNF-α In Serum And Cerebrospinal Fluid In Children With Viral Encephalitis

BackgroundViral encephalitis(VE)is a common infectious disease caused by viral infection in Pediatrics.Its clinical manifestation is usually nonspecific in the early stage,such as fever,sore throat,abdominal pain or respiratory symptoms,followed by headache,vomiting,late drowsiness,disorientation,severe convulsions,coma and other neurological symptoms in the late stage,and even death or with serious sequela in severe cases.The virus can damage the neurons directly or indirectly,and the most common pathological changes are neuronal edema,degeneration,focal necrosis,nodular proliferation of glial cells,as well as aggregation of parenchymal cells,perivascular macrophages and lymphocytes.Tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)are the major inflammatory cytokines with multiple biological functions,which may play important roles in this pathological process.There were multiple previous studies focused on inflammatory mediators of VE at home and abroad.Relationships of IL-6 and TNF-a in cerebrospinal fluid(CSF)with the pathogenesis of VE in children are mostly discussed,however,there are few studies on changes of IL-6 and TNF-α in mild and severe types of VE in serum/CSF,as well as the effect of gamma-globulin on their expressions.Therefore,the study was conducted to explore the mechanism of VE by detecting the levels of TNF-α and IL-6,so as to provide a new approach for clinical diagnosis and treatment of VE.ObjectiveAim to study the relationship of the expression levels of IL-6 and TNF-α in serum and CSF with the severity of the disease in children with VE,and to investigate the effect of gamma-globulin treatment on the expression of the two inflammatory factors.Methods1.From October 2013 to May 2015,a total of 30 hospitalized children with VE were treated in the First Affiliated Hospital of Henan University of Science and Technology.According to the severity of the disease,the enrolled 30 cases were further divided into mild group of VE and the severe group.At the same time,10 children admitted in the Department of pediatrics of the same hospital were served as the control group.2.The informed consent was signed by the parents before CSF collection via lumbar puncture.Meanwhile,the study was approved by the ethics committee of the hospital.3.Therapeutic method:There was no specific antiviral therapy in children with VE,mainly for symptomatic supportive treatment,including physical cooling,sedation and anti-convulsion,dehydration,reduction of intracranial pressure,and improvement of brain metabolism,as well as the proper use of glucocorticoids.In the severe group,all the 10 cases were managed with IVIG.4.Serum and CSF specimens were collected in each group within 24 hours after admission.In strict accordance with the aseptic operation,2ml serum and CSF were taken from each subject,respectively,and then frozen in refrigerator for examination.Specimens of CSF mixed with blood were abandoned.In mild group and severe group,2ml serum and CSF specimens were collected again 10-14 days after treatment,respectively,and were stored in the refrigerator for further detection.Specimens were thawed at room temperature and centrifuged at 3000/min for 10 min.Furthermore,supernatant(1ml)was taken for measuring the levels of IL-6 and TNF-a in serum and CSF by ELISA method.5.Data processing and analysis were performed with the statistical software program SPSS 19.0.Measurement data were expressed as mean ± standard deviation(x ±S).Comparison of mean in multiple groups was conducted with analysis of variance.Pairwise comparison of mean was done with independent sample t test.P<0.05 was considered that the difference was significant.Results1.Before treatment,serum levels of IL-6 and TNF-a were significantly higher in mild group and severe group than those in control group(P<0.01),meanwhile,serum levels of IL-6 and TNF-a in severe group were remarkably higher than those in mild group(P<0.05),with statistical differences.In addition,there were statistical differences that levels of IL-6 and TNF-a in CSF of mild and severe groups were obviously upregulated than those of control group before treatment,and both of which were higher in severe group than those in mild group(P<0.05).2.Compared with levels before treatment,serum levels of IL-6 and TNF-a were decreased in mild group after treatment,but there was no significant difference(P>0.05).Besides,statistical difference was found that levels of serum IL-6 and TNF-a were reduced significantly in severe group after treatment than those before treatment(P<0.05).After treatment,serum levels of IL-6 and TNF-α in severe group remained higher than those in mild group and control group(P<0.05),indicating statistical differences.3.Comparison between mild group and severe group reveled that levels of IL-6 and TNF-a in CSF of severe group were higher than those in mild group,and the difference was statistically significant(P<0.05).Conclusion1.Inflammatory mediators IL-6 and TNF-a in serum and CSF are involved in the pathogenesis of VE,and their expression levels may be associated with the severity of the disease.2.IL-6 and TNF-α expressions in serum and CSF are decreased following the application of gamma-globulin in children with severe VE,suggesting that gamma-globulin may play a therapeutic role in down-regulating inflammatory mediators;the inflammatory mediators in the CSF with severe VE has indicated that long-term presence of immune inflammatory response may be related to the degree of nerve injury.