The Clinical Significance Of IFN-γ, IL-10 And TGF-β₁ Levels Detected In Patients With Viral Hepatitis B

Objective: Cytokines are the polypeptides which are excreted by mononuclear macrophage et al. They accommodate the function of cells. Some of cytokines accommodate the immune response of lymphocyte. They not only aggravate the inflammation and necrosis of hepatic cell, but also activate interstitial cell, promote the composition, excretion and deposition of the extracellular matrix (ECM), and lead to hepatic fibrosis and liver cirrhosis. Therefore, cytokines play an important role in the development of Viral Hepatitis B. The patients with acute hepatitis B, chronic hepatitis B (mild, moderate and severe), liver cirrhosis and normal control were used as the objects in the study. The serum levels of IFN-γ, IL-10 and TGF-β1 were observed in different clinical developmental stage. The relation between the three cytokines and the chronicity of AHB and the process of hepatic fibrosis were discussed in the development of viral hepatitis B. In the end, the theoretical evidence and new therapy are provided for clinical curing viral hepatitis B and hepatic fibrosis with cytokines.Methods: Seventy patients with viral hepatitis B were selected in the third hospital affiliated to Hebei Medical University and the fifth hospital of Shijiazhuang city from November, 2005 to May, 2006. There were 47 men and 23 women among them. Their average age was 45.53. There were 6 patients with acute hepatitis B (AHB), 15 patients with mild chronic hepatitis B (CHBⅠ), 17 patients with moderate hepatitis B (CHBⅡ), 14 patients with severe hepatitis B (CHBⅢ) and 18 patients with liver cirrhosis (LC) among them. In addition, 18 healthy people were used as the normal controls (NC) who were 12 men and 6 women. Their average age was 44.17. There was no difference in sex and age between the patients and the healthy people. After 4ml blood in ulnar vein were taken, the serum levels of PCⅢ, CⅣ, HA and LN were detected by RIA. The liver function and PTA were detected. HBV-DNA was detected by PCR. The serum levels of IFN-γ, IL-10 and TGF-β1 were detected by ELISA. Statistics work was done with SPSS 13.0 statistical software.Results: (1) The results of serum IFN-γ, IL-10 and TGF-β1 in 70 patients with Viral Hepatitis B and normal control: There were no differences about serum IFN-γbetween the NC and the LC group and between the CHBⅠand the CHBⅡgroup, but significant differences among the rest groups (P<0.05 and P<0.01); There were no differences about serum IL-10 between the CHBⅠand the CHBⅡgroup and between the CHBⅢand the LC group, but significant differences among the rest groups (P<0.05 and P<0.01); There were no differences about serum TGF-β1 between the CHBⅡand CHBⅢgroup, but significant differences among the rest groups (P<0.05 and P<0.01). Accompanied with the disease aggravation in CHB and LC group, the serum level of IFN-γgradually decreased, but the serum levels of IL-10 and TGF-β1 gradually increased. It was discovered that there was a significant negative correlation between the serum level of IFN-γand the degree of aggravation (r=-0.759, P<0.01). In contrast, there was a significant positive correlation between the serum levels of IL-10 and TGF-β1 and the degree of aggravation (r=0.516, r=0.785, P<0.01). (2) The results of serum Th1/Th2 cytokines in patients with AHB, patients with CHB and normal control: The serum Th1/Th2 cytokines in patients with AHB was significantly higher than the patients with CHB and normal control (P<0.01).The serum Th1/Th2 cytokines in patients with CHB was significantly lower than the normal control (P<0.05). (3) The results of serum PCⅢ, CⅣ, HA, LN, ALT, TBIL, ALB and PTA in 70 patients with Viral Hepatitis B and normal control: There were no significant differences about serum PCⅢbetween the NC and the AHB group and between the AHB and the CHBⅠgroup, about serum CⅣbetween the AHB and CHBⅢgroup, about serum LN between the NC and the CHBⅠgroup and between the AHB and the CHBⅢgroup, about serum ALT between the CHBⅡand the CHBⅢgroup, about serum TBIL between the AHB and the CHBⅡgroup, about serum ALB between the NC and the AHB group, or about serum PTA among the NC, the AHB or the CHBⅠgroup. Besides, there were significant differences among the rest groups (P<0.05 and P<0.01). (4) The correlation between serum IFN-γ, IL-10 and TGF-β1 and PCⅢ, CⅣ, HA, LN, ALT, TBIL, ALB and PTA in patients with CHB and LC: There was a significant negative correlation between the serum level of IFN-γand the serum levels of TBIL, PCⅢ, CⅣ, HA and LN (r=-0.704, r=-0.648, r=-0.744, r=-0.822 and r=-0.592, P<0.01). However, there was a significant positive correlation between the serum level of IFN-γand the serum levels of ALB and PTA (r=0.547 and r=0.693, P<0.01). Furthermore, there was a significant positive correlation between the serum level of IL-10 and the serum levels of TBIL and HA (r=0.366 and r=0.374, P<0.01). However, there was a significant negative correlation between the serum level of IL-10 and the serum levels of ALB and PTA (r=-0.655 and r=-0.564, P<0.01). Finally, there was a significant positive correlation between the serum level of TGF-β1 and the serum levels of TBIL, PCⅢ, CⅣ, HA and LN (r=0.701, r=0.649, r=0.552, r=0.642 and r=0.521, P<0.01). However, there was a significant negative correlation between the serum level of TGF-β1 and the serum levels of ALB and PTA (r=-0.577 and r=-0.607, P<0.01). (5) The correlation between serum HBV-DNA and serum IFN-γ, IL-10, TGF-β1, PCⅢ, CⅣ, HA and LN in patients with CHB and LC: The serum level of IL-10 and TGF-β1 in the patients with HBV-DNA+ group was significantly higher than the patients with HBV-DNA- group (P<0.01). With the serum level of HBV-DNA stepping up, the serum level of IL-10 and TGF-β1 also gradually stepped up. That was opposite for the serum level of IFN-γ. The serum level of PCⅢ, CⅣ, HA and LN in the patients with HBV-DNA+ group was significantly higher than the patients with HBV-DNA- group (P<0.05 and P<0.01). (6) The correlation among serum IFN-γ, IL-10 and TGF-β1 in patients with AHB, CHB and LC: There was a significant negative correlation between the serum level of IFN-γand the serum level of IL-10 and TGF-β1 (r=-0.412 and r=-0.628, P<0.01). Moreover, there was a significant positive correlation between the serum level of IL-10 and the serum level of TGF-β1 (r=0.370, P<0.01).Conclusion: The serum IFN-γ, IL-10 and TGF-β1 of the patients with viral hepatitis B correlate with the liver damage and the liver functional level. They not only reflect the degree of injury in the hepatic cells but also correlate intimately with the formation of hepatic fibrosis. The serum level variations of IFN-γ, IL-10 and TGF-β1 correlate with the duplication and persistent infection of HBV. Therefore, the determination of serum HBV-DNA and some cytokines plays an important and practical role in the development of viral hepatitis B, the process of hepatic fibrosis and the evaluation of curative effect and progn.