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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 level of peak plasma IL-12, p40 (A), and peak IL-12/p40 ratio (B) between virological responders (VRs) and nonvirological responders (NVRs) after combined therapy. Peak plasma IL-12 and peak IL-12/p40 were mostly detected from 6 (T6) to 10 (T10) months in 12 CHB carriers treated with combined therapy. The statistical analysis was done by Mann-Whitney U test.
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Figure 3: The level of peak plasma IL-12, p40 (A), and peak IL-12/p40 ratio (B) between virological responders (VRs) and nonvirological responders (NVRs) after combined therapy. Peak plasma IL-12 and peak IL-12/p40 were mostly detected from 6 (T6) to 10 (T10) months in 12 CHB carriers treated with combined therapy. The statistical analysis was done by Mann-Whitney U test.

Mentions: When the peak level of IL-12 was compared between VRs and NVRs, VRs showed approximately a 2-fold higher level of peak plasma IL-12 than NVRs, albeit this was marginally significant (218.0±41.4 vs. 108.1±28.6 pg/ml, respectively; AVR±SEM; p=0.09, Mann-Whitney U) (Fig. 3A). Interestingly, VRs exhibited a significantly higher IL-12/p40 ratio than NVRs (5.35±1.38 vs. 1.80±0.29, respectively; AVR±SEM, p<0.05 Mann-Whitney U) (Fig. 3B). It is worth noting that there is no significant difference in pretreatment levels of plasma IL-12 and IL-12/p40 ratios between VRs and NVRs. Our result is somehow similar to the previous reports that murine recombinant IL-12 (rIL-12) can efficiently suppress HBV replication in transgenic mice (10) and that the recovery from CHB by IFN-α treatment depends on the level of serum IL-12 (9). More importantly, human rIL-12 protein administered subcutaneously inhibits viral replication in CHB patients with a peak serum level of IL-12 (173 pg/ml), which is similar to the peak IL-12 level (163.1 pg/ml) induced in this study (11).


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 level of peak plasma IL-12, p40 (A), and peak IL-12/p40 ratio (B) between virological responders (VRs) and nonvirological responders (NVRs) after combined therapy. Peak plasma IL-12 and peak IL-12/p40 were mostly detected from 6 (T6) to 10 (T10) months in 12 CHB carriers treated with combined therapy. The statistical analysis was done by Mann-Whitney U test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: The level of peak plasma IL-12, p40 (A), and peak IL-12/p40 ratio (B) between virological responders (VRs) and nonvirological responders (NVRs) after combined therapy. Peak plasma IL-12 and peak IL-12/p40 were mostly detected from 6 (T6) to 10 (T10) months in 12 CHB carriers treated with combined therapy. The statistical analysis was done by Mann-Whitney U test.
Mentions: When the peak level of IL-12 was compared between VRs and NVRs, VRs showed approximately a 2-fold higher level of peak plasma IL-12 than NVRs, albeit this was marginally significant (218.0±41.4 vs. 108.1±28.6 pg/ml, respectively; AVR±SEM; p=0.09, Mann-Whitney U) (Fig. 3A). Interestingly, VRs exhibited a significantly higher IL-12/p40 ratio than NVRs (5.35±1.38 vs. 1.80±0.29, respectively; AVR±SEM, p<0.05 Mann-Whitney U) (Fig. 3B). It is worth noting that there is no significant difference in pretreatment levels of plasma IL-12 and IL-12/p40 ratios between VRs and NVRs. Our result is somehow similar to the previous reports that murine recombinant IL-12 (rIL-12) can efficiently suppress HBV replication in transgenic mice (10) and that the recovery from CHB by IFN-α treatment depends on the level of serum IL-12 (9). More importantly, human rIL-12 protein administered subcutaneously inhibits viral replication in CHB patients with a peak serum level of IL-12 (173 pg/ml), which is similar to the peak IL-12 level (163.1 pg/ml) induced in this study (11).

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