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Hepatitis C virus (HCV) is an important cause of acute and chronic hepatitis which is a disorder with a high worldwide prevalence. HCV core protein was considered as immunogenic counterpart of the HCV vaccine and it is an ideal candidate for HCV vaccine. Since cytokines such as IL-6, TNF-alpha and IFN-Gamma are responsible for the prevention of viral infection, this study aimed to evaluate the effectiveness of HCV core protein as a vaccine. Ten BALB/c mice were immunized with HCV core protein and after 42 days the splenocytes were isolated and the IL-6 and INF-gamma secretion were measured using ELISpot technique, at the same time TNF-alpha was determined by ELISA in the sera. The MTT assay was done to assess the viability of the cultured splenocytes. For evaluating the humoral immune response against the recombinant HCV core protein the DOT Blot test was used. Data was compared using one-way ANOVA test and significant results were considered at p < 0.05. In the present study the IL-6, INF-gamma and TNF-alpha levels were dramatically higher in the immunized mice compared to the control group (respectively, 22.9 +/- 1.26; 18.53 +/- 3.87; 53.96 +/- 4.54 and p < 0.05). The immunized mice with recombinant HCV core protein showed higher amount of IL-6, INF-gamma and TNF-alpha in the current study. Since the level of IL-6, TNF-alpha and IFN-gamma is high in patients with acute HCV infection, thus a vaccine which could stimulate the secretion of these cytokines in advance may have a preventive role.