The Effect Of Lamivudine Treatment On Cellular Immune Responses In Patients With Hepatitis B

Objective l.To detect the levels of IL-10 and IFN- Y in culture?supernatants of peripheral blood mononuclear cells ( PBMC) in patients with chronic hepatitis B,and to analyse their relation with the grades of intrahepatic inflammation,the amounts of HBV DNA load and the presence of HBeAg in serum. 2.To study the effect of the levels of IFN-Y and IL-10 in the supernatants of PBMC cultures in CHB patients treated with lamivudine. 3.To demonstrate whether antiviral treatments able to inhibit viral replication and to reduce viral and antigen load can successfully resconstitute CTL responses in CHB patients. Methods l.PBMCs of 43 chronically HBV-infected individuals and 10 healthy donors were stimulated with rHBcAg or PHA,IL-10 and IFN- Y production were determined by ELISA after 72h cultivation. 2.Before lamivudine therapy.and at 1,3,6,and 9 months during lamivudine therapy.the production of IL-10 and IFN-Y in culture supernatants of PBMCs from 26 cases were detected by ELISA as above described. 3.During lamivudine or interferon- a treatment,PBMCs were separated routinely.and stimulated by peptide HBcAgl8-27/rHBcAg/rIL-2,the cytotoxic activity against HBV DNA transfected hepatoma cells(HepG2.2.15) and HepG2 cells were detected by lactate dehydrogenase(LDH) assay after 21 days cultivation. Results l.The production of IFN- Y in patients with high amounts of HBV DNA,or with the presence of HBeAg in serum is less than those with low amounts of HBV DNA or without HBeAg in serum,but on the way round for IL-10.The levels of IFN- Y secreted by HBV antigen specific T cells among patients with different grades of intrahepatic inflammation have no significant difference,but IL-10 production is higher in patients who have mild or moderate liver injury than those with severe liver injury. 2.During lamivudine treatment,the levels of IFN- Y were increased at1,3,6,and 9 months(p<0.05),however,the levels of IL-10 were decreased slightly(p>0.05).In patients with complete or part response to lamivudine,the levels of IFN- Y increased significant than that of pre-therapy with lamivudine,and the levels of IL-10 decreased obviously only in patients with complete responses to lamivudine. 3. Although still weaker than patients with acute hepatitis B.the cytotoxic activities against HepG2.2.15 cells were increased by whether lamivudine or interferon- a treatment which have not obviously effect on the cytotoxic activities against HepG2 cells.During lamivudine treatment.the HBV-specific cytotoxic T cell activity was increased strikingly at the first month,and reached maximal level at the third month,then dropped gradually.to the sixth month,we could not find obviously change compared with pre-therapy.Unsimilar to therapy with lamivudine,the HBV-specific CTL activity was enhanced significantly even at the sixth month during interferon- a treatment. Conclusion l.The presence of high amounts of HBV DNA and HBeAg in serum suppressed the production of IFN- Y .while enhanced the production of IL-10.The grades of intrahepatic inflammation is negatively correlated with the production of IL-10. 2.Lamivudine treatment can promote a Thl type cytokine-mediated immune responses in patients with complete or part responses to lamivudine. 3.Treatment with lamivudine can restore HBV-specific CTL activity transiently.