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Increase of Plasma IL-12/p40 Ratio Induced by the Combined Therapy of DNA Vaccine and Lamivudine Correlates with Sustained Viremia Control in CHB Carriers.

Im SJ, Yang SH, Yoon SK, Sung YC - Immune Netw (2009)

Bottom Line: Twelve CHB carriers were intramuscularly immunized 12 times at a 4-week interval with 8 mg of HBV DNA vaccine during the standard lamivudine treatment (100 mg/daily/1 year).Six out of 12 CHB carriers revisited the clinic, and their HBV DNA levels were examined.In addition, there was no significant temporal correlation between the peak IL-12/p40 ratio and the elevation of serum alanine aminotransferase (ALT) in this study, contrast to IFN-alpha therapy which induced peak IL-12 level following ALT flares.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular and Life Sciences, Pohang University of Science & Technology, Pohang, Korea.

ABSTRACT

Background: We previously reported that IFN-gamma producing T cell responses induced by the combined therapy of DNA vaccine and lamivudine for one year are important for the induction of sustained virological response (SVR). However, IFN-gamma production is not sufficient to predict sustained viremia control in chronic hepatitis B (CHB) carriers treated.

Methods: Twelve CHB carriers were intramuscularly immunized 12 times at a 4-week interval with 8 mg of HBV DNA vaccine during the standard lamivudine treatment (100 mg/daily/1 year). The level of cytokines during and after the combined therapy in plasma of all 12 CHB carriers treated was determined by each ELISA kit. Six out of 12 CHB carriers revisited the clinic, and their HBV DNA levels were examined.

Results: The combined therapy increased plasma IL-12 and IL-12/p40 ratio during the treatment (baseline vs. peak level: 41.8+/-8.3 vs. 163.1+/-29.2 pg/ml; p<0.01 and 0.96+/-0.25 vs. 3.58+/-0.86; p<0.01, espectively), and the peak level of plasma IL-12 and IL-12/p40 ratio was evoked at 6 to 10 months during the combined therapy. In particular, CHB carriers with SVR had two and three-fold higher level of the peak plasma IL-12 and plasma IL-12/p40 ratio than non-virological responders (NVRs), respectively (218.0+/-41.4 vs. 108.1+/-28.6 pg/ml; p=0.09 and 5.35+/-1.38 vs. 1.80+/-0.29; p<0.05, respectively), while p40 level was consistent during the combined therapy. In addition, there was no significant temporal correlation between the peak IL-12/p40 ratio and the elevation of serum alanine aminotransferase (ALT) in this study, contrast to IFN-alpha therapy which induced peak IL-12 level following ALT flares.

Conclusion: Our results indicate that the combined therapy induces the increase of plasma IL-12 and IL-12/p40 ratio, which are associated with long-term SVR in CHB carriers.

No MeSH data available.


Related in: MedlinePlus

The longitudinal analysis of the level of serum ATL and IL-12/p40 ratio in virological responders during the combined therapy. The kinetics of serum ALT levels (closed circles) and IL-12/p40 ratio (open circles) in VRs was compared in parallel to examine the temporal correlation between them.
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Figure 4: The longitudinal analysis of the level of serum ATL and IL-12/p40 ratio in virological responders during the combined therapy. The kinetics of serum ALT levels (closed circles) and IL-12/p40 ratio (open circles) in VRs was compared in parallel to examine the temporal correlation between them.

Mentions: In contrast to IFN-α therapy which induced hepatitis flares in 8 out of 10 VRs, followed by peak IL-12 level (9), the elevation of alanine aminotransferase (ALT) level was generated in 2 out of 6 VRs during the treatment, and only one patient (V#118) showed concomitant elevation of ALT level with the increased IL-12/p40 ratio (Fig. 4), reflecting that there was no significant temporal correlation between the increase of plasma IL-12 and an ALT flare in this study. These results indicate that our combined therapy could suppress viral replications presumably by the increased IL-12 without massive hepatocytolysis.


Increase of Plasma IL-12/p40 Ratio Induced by the Combined Therapy of DNA Vaccine and Lamivudine Correlates with Sustained Viremia Control in CHB Carriers.

Im SJ, Yang SH, Yoon SK, Sung YC - Immune Netw (2009)

The longitudinal analysis of the level of serum ATL and IL-12/p40 ratio in virological responders during the combined therapy. The kinetics of serum ALT levels (closed circles) and IL-12/p40 ratio (open circles) in VRs was compared in parallel to examine the temporal correlation between them.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2803296&req=5

Figure 4: The longitudinal analysis of the level of serum ATL and IL-12/p40 ratio in virological responders during the combined therapy. The kinetics of serum ALT levels (closed circles) and IL-12/p40 ratio (open circles) in VRs was compared in parallel to examine the temporal correlation between them.
Mentions: In contrast to IFN-α therapy which induced hepatitis flares in 8 out of 10 VRs, followed by peak IL-12 level (9), the elevation of alanine aminotransferase (ALT) level was generated in 2 out of 6 VRs during the treatment, and only one patient (V#118) showed concomitant elevation of ALT level with the increased IL-12/p40 ratio (Fig. 4), reflecting that there was no significant temporal correlation between the increase of plasma IL-12 and an ALT flare in this study. These results indicate that our combined therapy could suppress viral replications presumably by the increased IL-12 without massive hepatocytolysis.

Bottom Line: Twelve CHB carriers were intramuscularly immunized 12 times at a 4-week interval with 8 mg of HBV DNA vaccine during the standard lamivudine treatment (100 mg/daily/1 year).Six out of 12 CHB carriers revisited the clinic, and their HBV DNA levels were examined.In addition, there was no significant temporal correlation between the peak IL-12/p40 ratio and the elevation of serum alanine aminotransferase (ALT) in this study, contrast to IFN-alpha therapy which induced peak IL-12 level following ALT flares.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular and Life Sciences, Pohang University of Science & Technology, Pohang, Korea.

ABSTRACT

Background: We previously reported that IFN-gamma producing T cell responses induced by the combined therapy of DNA vaccine and lamivudine for one year are important for the induction of sustained virological response (SVR). However, IFN-gamma production is not sufficient to predict sustained viremia control in chronic hepatitis B (CHB) carriers treated.

Methods: Twelve CHB carriers were intramuscularly immunized 12 times at a 4-week interval with 8 mg of HBV DNA vaccine during the standard lamivudine treatment (100 mg/daily/1 year). The level of cytokines during and after the combined therapy in plasma of all 12 CHB carriers treated was determined by each ELISA kit. Six out of 12 CHB carriers revisited the clinic, and their HBV DNA levels were examined.

Results: The combined therapy increased plasma IL-12 and IL-12/p40 ratio during the treatment (baseline vs. peak level: 41.8+/-8.3 vs. 163.1+/-29.2 pg/ml; p<0.01 and 0.96+/-0.25 vs. 3.58+/-0.86; p<0.01, espectively), and the peak level of plasma IL-12 and IL-12/p40 ratio was evoked at 6 to 10 months during the combined therapy. In particular, CHB carriers with SVR had two and three-fold higher level of the peak plasma IL-12 and plasma IL-12/p40 ratio than non-virological responders (NVRs), respectively (218.0+/-41.4 vs. 108.1+/-28.6 pg/ml; p=0.09 and 5.35+/-1.38 vs. 1.80+/-0.29; p<0.05, respectively), while p40 level was consistent during the combined therapy. In addition, there was no significant temporal correlation between the peak IL-12/p40 ratio and the elevation of serum alanine aminotransferase (ALT) in this study, contrast to IFN-alpha therapy which induced peak IL-12 level following ALT flares.

Conclusion: Our results indicate that the combined therapy induces the increase of plasma IL-12 and IL-12/p40 ratio, which are associated with long-term SVR in CHB carriers.

No MeSH data available.


Related in: MedlinePlus