Limits...
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

(A, B) Serial analysis of the average level of plasma IL-12, p40 (A), and IL-12/p40 ratio (B) (mean±SEM) in CHB carriers during and after the combined therapy of DNA vaccine plus lamivudine. The level of plasma IL-12 and p40 was determined by a specific ELISA. (*p<0.05, **p<0.01 by Wilcoxon signed rank test) (C-E) The level of plasma IL-12 (C), p40 (D), and IL-12/p40 ratio (E) in each subject was shown before the treatment (pre, T0), the peak level detected during the combined therapy (peak, usually T6 to T10), and at the end of treatment (end, T12).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2803296&req=5

Figure 2: (A, B) Serial analysis of the average level of plasma IL-12, p40 (A), and IL-12/p40 ratio (B) (mean±SEM) in CHB carriers during and after the combined therapy of DNA vaccine plus lamivudine. The level of plasma IL-12 and p40 was determined by a specific ELISA. (*p<0.05, **p<0.01 by Wilcoxon signed rank test) (C-E) The level of plasma IL-12 (C), p40 (D), and IL-12/p40 ratio (E) in each subject was shown before the treatment (pre, T0), the peak level detected during the combined therapy (peak, usually T6 to T10), and at the end of treatment (end, T12).

Mentions: To investigate alterations of immunological characteristics as indicators to predict SVR by the combined therapy, the level of plasma IL-12, p40, IL-4, IL-2, and IFN-γ was monitored longitudinally in each individual by a specific ELISA assay. Among cytokines analyzed, only IL-12 and p40 were detectable. The highest level of plasma IL-12 (163.1±29.2 pg/ml; mean±SEM) was observed 6 to 10 months after combined therapy and was 4-fold higher than pretreatment level on the average (baseline vs. peak level; 41.8±8.3 pg/ml vs. 163.1±29.2 pg/ml; mean±SEM; p<0.01, Wilcoxon signed rank test) (Fig. 2A, C). However, it tended to return to basal levels thereafter. On the other hand, p40, which is known as a natural antagonist against IL-12, was not significantly changed regardless of the treatment except one patient (V#112) (Fig. 2A, D). Similar to plasma IL-12, elevation of the IL-12/p40 ratio (3.58±0.86 from 0.96±0.25, mean±SEM) was detected 6 to 10 months after combined therapy (p<0.01, Wilcoxon signed rank test) (Fig. 2B, E). In an independent experiment, no significant change in plasma IL-12 and IL-12/p40 ratio appeared in any of the 5 CHB carriers treated with lamivudine alone (data not shown), indicating that the increase of plasma IL-12 and IL-12/p40 ratio appears to be associated with DNA vaccine in combination with lamivudine treatment.


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)

(A, B) Serial analysis of the average level of plasma IL-12, p40 (A), and IL-12/p40 ratio (B) (mean±SEM) in CHB carriers during and after the combined therapy of DNA vaccine plus lamivudine. The level of plasma IL-12 and p40 was determined by a specific ELISA. (*p<0.05, **p<0.01 by Wilcoxon signed rank test) (C-E) The level of plasma IL-12 (C), p40 (D), and IL-12/p40 ratio (E) in each subject was shown before the treatment (pre, T0), the peak level detected during the combined therapy (peak, usually T6 to T10), and at the end of treatment (end, T12).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: (A, B) Serial analysis of the average level of plasma IL-12, p40 (A), and IL-12/p40 ratio (B) (mean±SEM) in CHB carriers during and after the combined therapy of DNA vaccine plus lamivudine. The level of plasma IL-12 and p40 was determined by a specific ELISA. (*p<0.05, **p<0.01 by Wilcoxon signed rank test) (C-E) The level of plasma IL-12 (C), p40 (D), and IL-12/p40 ratio (E) in each subject was shown before the treatment (pre, T0), the peak level detected during the combined therapy (peak, usually T6 to T10), and at the end of treatment (end, T12).
Mentions: To investigate alterations of immunological characteristics as indicators to predict SVR by the combined therapy, the level of plasma IL-12, p40, IL-4, IL-2, and IFN-γ was monitored longitudinally in each individual by a specific ELISA assay. Among cytokines analyzed, only IL-12 and p40 were detectable. The highest level of plasma IL-12 (163.1±29.2 pg/ml; mean±SEM) was observed 6 to 10 months after combined therapy and was 4-fold higher than pretreatment level on the average (baseline vs. peak level; 41.8±8.3 pg/ml vs. 163.1±29.2 pg/ml; mean±SEM; p<0.01, Wilcoxon signed rank test) (Fig. 2A, C). However, it tended to return to basal levels thereafter. On the other hand, p40, which is known as a natural antagonist against IL-12, was not significantly changed regardless of the treatment except one patient (V#112) (Fig. 2A, D). Similar to plasma IL-12, elevation of the IL-12/p40 ratio (3.58±0.86 from 0.96±0.25, mean±SEM) was detected 6 to 10 months after combined therapy (p<0.01, Wilcoxon signed rank test) (Fig. 2B, E). In an independent experiment, no significant change in plasma IL-12 and IL-12/p40 ratio appeared in any of the 5 CHB carriers treated with lamivudine alone (data not shown), indicating that the increase of plasma IL-12 and IL-12/p40 ratio appears to be associated with DNA vaccine in combination with lamivudine treatment.

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