The Host Immune Response For Patients With The Chronic Hepatitis B During Treatment Of Antiviral And Immunomodulatory

Objective :To investigate the secretion of Th1 cell related cytokines IL-2, IFN-γ, TNF-βand Th2 cell secretion of cytokines IL-4, IL-6, IL-10 for patients with chronic hepatitis B (CHB), which treated to anti-virus B with adefovir dipivoxil and regulate immunation with thymosin, to explore anti-HBV immune response mechanisms of adefovir dipivoxil and thymosin.Method: Make use of three-color flow cytometry detected cytokines of Th1 cell secretion and cytokines of Th2 cell secretion which 22 cases enrolled in Phase IV clinical trial of adefovir dipivoxil IV and 19 cases that enrolled in thymosin of free treatment of patients with chronic hepatitis B, detection time is before treatment, after 12, 24 weekend and 13, 21 weekend of peripheral blood expression, which detected the serum HBV DNA,liver function and other target at the same time.Results:一,Adefovir dipivoxil and Thymosin treatment group conclusions:1,The cytokine levels of patients with Chronic hepatitis B are lower than the control group significantly, the differences were statistically significant at each time point after treated with adefovir dipivoxil and Thymosin, cytokine of levels Th1 and Th2 cell secretion than before treatment was significantly increased (p <0.05)2,The secretion of Th1/Th2 cytokines have much more difference significantly in different stages of treatment.3,Group which are added stimulants and inhibitor compare with control group, Th1/Th2 cytokine secretion have significant differences before and after treatment ,all of them have statistics significance.4,In the treatment of different stages, the detection of cytokines and ALT,HBV DNA have no relevance.二,Adefovir dipivoxil treatment group conclusions:1,Pretreatment, the detection of cytokines and AST have no correlation; Thetreatment for 12 weeks, IL-2, IFN, TNF, IL-10 and AST levels are negatively correlated; When had been treated for 24 weeks, the detection of cytokines and AST have no relevance.2,Pretreatment and treatment for 12 weeks, the detection of cytokines and HBV DNA have no relevance; When had been treated for 24 weeks, TNF and HBV DNA have the positive correlation.3,Analysis by serological response:Treatment for 12 weeks:1) The cytokines level of completely response group compared with pre-treatment was significantly increased (P<0.05);2) Only Th2 cytokine secretion of IL-4, IL-6 which is Partial response group, had significant difference compared with pretreatment, but various cytokines increased than before treatment.3) Cytokine level of None-response group has growth trends than pretreatment, compared with before treatment has no statistically significance.Treatment for 24 weeks:1) The cytokine level of completely response group has upward trend compared with treated for 12 weeks, and increased significantly (P<0.001) than pretreatment, the cytokines levels treated for 24 weeks compared with treated for 12 weeks still has statistically significance.2) Partial response group compared with before treatment, the levels of cytokines increased than pretreatment, However, only IL-6 has statistics significance, compared with treated 12 weeks has no statistics significance; Completely response group'cytokine levels compared with partial response group, has no significant differences and has no statistics significance.These results suggest : from all sources completely response group cytokine levels with Partial response group were significant differences,complete response group Th1 cells secreting cytokines higher than partial response group, Th2 cell cytokine secretion was increased in partial response group. consider that cytokine levels can suggest antiviral treatment, particularly the cytokine of the secretion ofTh1 cells, But do not rule out the possibility that partial response group because the number of cases was less affected results.4,Biochemistry response:1) When had been treated for 12 weeks and 24 weeks, biochemistry completely response group'cytokine levels compared with pretreatment, secretion of Th1/Th2 cytokine levels before and after treatment were significantly different, both had statistics significance.2) When had been treated for 12 weeks, the biochemistry completely response group'secretion of Th1/Th2 cytokines and ALT had no relevance, secretion of Th1 cytokines IL-2, IFN, and TNF AST was negatively correlated, Th2 cytokine secretion of IL-10 and AST were negatively correlated; When had been treated for 24 weeks, biochemistry completely response group'IL-2, IL-10 and ALT were positively correlated, IL-2 and AST was positively correlated, IFN, IL-4 and AST were negatively correlated.3) When had been treated for 12 weeks, the biochemistry partial response group, only IL-6 has significant difference compared with before treatment, had statistics significance; When had been treated for 24 weeks, the biochemistry partial response group'various cytokine levels, compared with before treatment, had no significant difference and had no statistics significance. These results show that the chemistry of patients with complete response cytokines levels are higher than partial response group, consider that cytokine levels can suggest liver function; Cytokine levels of ALT, AST to a certain extent relevant, suggesting cytokine levels and liver inflammation are closely related. In particular cell secretion of Th1 cytokines.5,Virology response:1) When treated after 12 weeks, virology completely response group'secretion of Th1 and Th2 cytokines compared with before treatment, There was significant difference and statistics significance; When treated for 12 weeks, virology completely response group'Th1 cytokine secretion, IFN and ALT, AST was negatively related.IL-2, TNF and AST were negatively correlated; Whentreated for 24 weeks, virology completely response group virology cytokines and ALT, AST had no relevance.2) Virology partial response group'Th1 and Th2 secretion cytokines, except IL-2, the difference was significant, had statistics significance; Virology partial response group, ALT, AST, HBVDNA and Th1/Th2 cytokine secretion had no relevance.These results show : by virologic response analysis, viral load drop slowly group's cytokine levels significantly higher than that of viral load to resume normal group, according to virologic response analysis, Some suggest cytokine levels and ALT, AST has some correlation, consider it cytokine levels reflect the anti-virus treatment, the viral load changes, and liver inflammation reaction三,Thymosin treatment groups:1,Pretreatment and when had been treated for 13 weeks, various cytokines and AST have no relevance; 21 weeks of treatment, IL-2, TNF, and IL-10 are positively correlated with AST.2,Pretreatment, Th2 cell cytokine secretion of IL-10 and HBV DNA are relevant, But have no relevance when had been treated for 13 weeks.3,Biochemistry response:1) In the treatment of 13 weeks, biochemistry completely response group's cytokines IFN, TNF, IL-6, IL-10 compared with before treatment, biochemistry partial response group's various cytokines compared with before treatment, the difference was significant, have statistics significance. Non-responders compared before and after treatment, have no significant difference;2) In the treatment of 13 weeks, biochemistry completely response group's cytokines compare with partial response group, the difference was not significant and had no statistics significance. TNF and IL-10, completely response group compare with non-respons group, partial responds group compare with non-responds group, the difference was significant, had statistics significance.3) In the treatment of 26 weeks, the completely response group's IL-2, TNF, IL-6, IL-10 compare with before treatment, have statistics significance. Partialresponses group before and after treatment in various cytokines difference was significant, have statistics significance, completely response group, TNF, IL-6 compare with before treatment have statistics significance4) In the treatment of 26 weeks, Biochemistry completely response group and partial response group, None response group, the 3 Group's secretion of Th1/ Th2 cytokines, the difference was not significant, had no statistics significance.5) In the treatment of 13 weeks, Only the Biochemistry completely response group's Th2 cytokine secretion of IL-10 and ALT have relevance. In the treatment of 13 weeks and 26 weeks, the other various cytokines and ALT, AST, HBVDNA have no relevance.These results suggest : Response Group Th1 cytokine levels higher than the non-responders, No response Th2 cytokine levels higher than responders. Response by chemistry analysis, cytokine levels can react with the treatment effect.4,Virology response:In the treatment for 13 weeks:1) Virology completely response, partial responses, non-response group compared to February 2, secretion of Th1/Th2 cytokines was no significant difference, have no statistics significance. Partial responses before and after treatment. Non-response before and after treatment, the secretion of Th1/Th2 cytokine levels, the difference was significant, statistics significance. 2) Partial responders ALT and IL-6 were correlated with IFN-, IL-4, IL-6 and AST was positively correlated TNF, IL-10 and HBV DNA was negatively correlated, Unit non-response to the secretion of Th1 and Th2 cytokines and ALT, AST, HBV DNA without relevance.These results show : by virologic response analysis, viral load responders cytokine levels below some responders, Some responses group than non-responders, responders cytokine levels lower than non-responders, cytokines growth trends, and the therapeutic effect of a reverse trend, with thymosin mechanism of immune regulation, Cytokine levels can regulate immune responseeffect.Conclusion:1,The results of this paper show that, make use of PMA, monensin and ionomycin-cultured, could stimulate the secretion of cytokines secretion of cytoplasm and thereby enhanc cytokines fluorescence signal,conducive to the flow cytometric analysis of internal antigen detection.2,Patients with chronic hepatitis B by anti-virus treatment process Th1/Th2 cytokine secretion of the change, After adefovir dipivoxil show esters and thymosin the anti-virus treatment significant regulation of the expression of Th1 and Th2 cells, break the original immune tolerance of chronic hepatitis B patients ,reconstruct the immune function of the patients with chronic hepatitis B and. Restorat T cell function.3,The overall level, the secretion of Th1 and Th2 cytokines with ALT and HBV DNA have no relevance, that the level of cytokines can't reflect acute liver inflammation and the extent of viral replication;And reflect the chronic inflammation of the liver AST was relevant, cytokine levels in a certain extent reflect the chronic liver inflammation. adefovir dipivoxil group and the relevance of thymosin group, consider the specific mechanisms of different drugs.4,By serology, chemistry and virologic response analysis, suggesting that the Th1/Th2 cytokine expression levels of ALT, AST, HBVDNA have some relevance, which can reflect the extent of liver inflammation and virus replication,therefore, considering the secretion of Th1 and Th2 cytokines closely related to liver inflammation and replication of the virus after treatment with adefovir dipivoxil and thymosin antiviral.5,By analysis of the serological responses,the biochemistry responses and virologic response, cytokines of Th1/Th2 cell secretion reflect serological change ,liver function and the change of HBV DNA.6,Secretion of Th1 and Th2 cytokine expression levels, can be used as a treatment of chronic hepatitis B patients effect of a clinical monitoring indicators clearly immune state, suggesting that the prognosis of the illness and prognosis.