Dynamic Change Of Serum Interleukin-18 Levels And Polymorphisms Of Interleukin-18 Gene In Patients With Acute Cerebral Infarction

Objective To investigate the clinical significance of dynamic change of serum interleukin-18(IL-18) levels in acute cerebral infarction(ACI) patients,and to determine whether two single nucleotide polymorphisms(SNPs) located at -607 and -137 in the promoter region of IL-18 gene are associated with ACI.Methods Ninety-eight ACI patients and 100 healthy individuals with matched clinical data,such as age,sex,body mass index,cigarette-smoking and alcohol-drinking status,were recruited.The serum IL-18 levels in the patients with ACI on 1^st,10^th and 20^th day after the onset and in healthy subjects were measured by ELISA.Polymerase chain reaction with sequence specific primer(PCR-SSP) was used to genotype the SNPs of -607C/A and -137G/C in ACI patients and healthy controls.The correlations of the genotypes to risk of ACI and IL-18 expression were analyzed.Resultsâ‘ The serum IL-18 levels in ACI patients on 1^st and 10^th day were significantly higher than that in the healthy controls(F=254.567,q=34.211,16.388, P＜0.01).However,there was no significant difference between the serum IL-18 levels on the 20^th day in ACI patients and those of healthy controls.The serum IL-18 levels on the 1^st day were significantly higher than on the 10^th and 20^th day(q=17.734,32.777,P＜0.01), and those of 10^th day were also significantly higher than those of 20^th day(q=15.043, P＜0.01).â‘¡There were no significant difference in the distribution of genotypic frequencies and allelic frequency at position -607.The frequencies of -137 GG genotype was significantly higher in ACI patients(x²=5.667,P=0.017),while -137 GC was significantly decreased in ACI patients compared to the control groups(x²=4.559, P=0.033).Significant difference was also found in allelic frequency at position -137 between ACI patients and control(x²=5.322,P=0.021).â‘¢The -137 GC+CC genotype decrease the risk of ACI compared to GG genotype(OR=0.472,x²=5.667,P=0.017),but no significant correlation of -607 polymorphism to risk of ACI was found.â‘£ACI patients with -137 GG genotype had significantly higher serum IL-18 levels than those with GC+CC patients(t=2.082,P=0.040),but no significant difference was found between the genotypes in controls.The differences of serum IL-18 levels between the -607 genotypes in both ACI patients and controls were not significant.Conclusionâ‘ The elevated serum IL-18 levels and dynamic change of IL-18 levels in ACI patients suggest IL-18 may play an important role in pathogenesis of ACI and probably be a prognostic factor of ACI.â‘¡The IL-18 promoter gene polymorphism at position -607 is not associated with ACI,but the polymorphism at position -137 is associated with ACI and C allele may be protected against ACI.â‘£The genotypes at position -607 are not associated with serum IL-18 levels,whereas the C allele at position -137 may result in the decreased production of IL-18 protein in ACI patients.