Objectives: To study the relationship between intra-hepatic levels of regulated on activation, normal T-cell expressed and secreted (RANTES) and the disease severity and liver inflammatory degrees in patients with chronic hepatitis B and the possible mechanism of the changes of intra-hepatic levels of RANTES.
Methods: The expression of RANTES of the livers was studied using immunohistochemical stainings and morphometric quantitative measurements in liver specimens from 10 normal subjects and 64 patients with chronic hepatitis B with different degrees of liver inflammation and different clinical severity. The expressions of RANTES protein and mRNA in cell line HepG2, HepG2.2.15 and HepG2 treated with 10 ng/ml TNFa at different times were quantified by ELISA and one-step RT-PCR.
Results: The expression of RANTES of the livers in patients was significantly higher than that in the normal controls. Hepatic RANTES levels increased significantly and the increases were parallel to the increases of the severity of the hepatitis, from mild, moderate to severe hepatitis (the positive units were 3.7+/-1.5, 15.6+/-6.9, 24.0+/-4.0, 37.9+/-11.1, respectively) and from G0 degree to G4 degrees of liver inflammation (the positive units were 3.7+/-1.5, 15.0+/-5.7, 21.6+/-5.9, 30.3+/-8.2, 40.9+/-12.3, respectively). The expressions of RANTES protein and mRNA of HepG2.2.15 were higher than that of HepG2. RANTES protein and mRNA were induced in HepG2 by TNFa.
Conclusion: RANTES may have an important role in the pathogenesis of chronic hepatitis B. The elevation of hepatic RANTES may be caused by hepatitis B virus and TNFa.