Razi Journal of Medical Sciences

    Background & Aim: Multiple sclerosis(MS) is the most common inflammatory disease of central nervous system which is caused by an autoimmune process leading to destruction of myelin sheath. In this disease, CD4+ T–lymphocytes, mostly of TH1 phenotype, play important roles in destruction of neuronal tissues.  Because of the probable etiologic participation of EBV virus in immunopathogenesis of MS, the aim of this study was to evaluate the relationship between serum levels of anti-Epstein Barr virus antibodies and production of TH1 and TH2 cytokines.

Patients and Method: A descriptive study was performed on 68 MS patients in different stages of the disease and 20 healthy individuals. Blood samples were taken and plasma levels of anti-EBNA-1 and VCA antibodies were determined by ELISA method. Then, peripheral blood mononuclear cells (PBMC) were isolated by Ficoll Hipaque separation and stimulated with PHA in optimal culture conditions. Concentrations of IFN-γ, IL-12 and IL-4 in culture supernatants were then measured by ELISA. Statistical analysis was performed by using SPSS version 16. Mann-Whitney,  t-test,and Pearson correlation coefficient were used to compare  the  variables and find the correlation between them. P<0.005 was considered  statistically significant.

 Results: The mean levels of anti EBNA-1 and VCA antibodies were significantly higher in patients compared to controls (P=0.04, P=0.001 respectively). Concentrations of IFN-γ, IL-4 and  IL-12 were also significantly higher in MS patients than healthy individuals (P=0.001, P=0.005, p=0.002 respectively). Although the ratios of IFN-γ to IL-4 and IL-12 to IL-4 were higher in MS patients than healthy individuals, this increase did not reach a significant level (P>0.05). A statistically significant correlation was found between anti EBNA-1 and VCA antibodies and IL-12 production (P =0.02, r=0.27& P=0.04, r=0.25 respectively) whereas no significant correlation was found between these antibodies and production of IFN-γ and IL-4 in MS patients.

 Conclusion: The significant correlation between the level of anti-Epstein Barr virus antibodies and  IL-12 production in MS patients implies the probable role of this cytokine in skewing immune responses toward  TH1 phenotype. It is possible that this putative viral agent in combination with other etiological agents is involved in the etiology and progression of the disease.