HBV replication is significantly reduced by IL-6

Abstract

Interleukin-6 (IL-6) is a pleiotropic cytokine with pivotal functions in the regulation of the biological responses of several target cells including hepatocytes. The level of serum IL-6 has been reported to be elevated in patients with chronic hepatitis B, cirrhosis and hepatocellular carcinoma and represents the best marker of HBV-related clinical progression as compared with several other cytokines. In this study, we found that IL-6 was able to effectively suppress hepatitis B virus (HBV) replication and prevent the accumulation of HBV covalently closed circular DNA (cccDNA) in a human hepatoma cell line. We also demonstrated that the suppression of HBV replication by IL-6 requires concurrently a moderate reduction of viral transcripts/core proteins and a marked decrease in viral genome-containing nucleocapsids. Studies on the stability of existing viral capsids suggest that the IL-6 effect on the reduction of genome-containing nucleocapsids is mediated through the prevention of the formation of genome-containing nucleocapsids, which is similar to the effect of interferons. However, IFN-α/β and IFN-γ did not participate in the IL-6-induced suppression of HBV replication. Taken together, our results will provide important information to better understand the role of IL-6 in the course of HBV infection.

KIR and a specific HLA-C gene are associated with susceptibility and resistance to hepatitis B virus infection in a Brazilian population

“…9 Serum levels of IL-6 were also increased in OBI cases (17.161.1 pg/ml) and HBV carriers (18.461.3 pg/ml) compared to SHRs (7.861.0 pg/ml) (P,0.05). Serum IL-6 levels have been reported to be elevated in individuals with chronic hepatitis B infection, cirrhosis and hepatocellular carcinoma, 10 and serum IL-6 levels were in agreement with this reported relationship between this cytokine and the progression of HBV infection. INF-c and IL-2 serum levels increased in SHRs (175.76 1.0 pg/ml and 15.261.9 pg/ml, respectively) compared to HBV carriers (58.362.8 pg/ml and 8.261.7 pg/ml, respectively) and OBI cases (62.361.1 pg/ml and 7.761.3 pg/ml, respectively).…”

“…Indeed, circulatory TNF-a levels increase during HBV infection, 10 and increased hepatic TNF-a production is associated with the suppression of HBV replication in transgenic mice expressing HBV in the liver. 12 Altogether, the NK cell activity, HBcAg-specific T-cell responses and cytokine patterns observed in this study suggest that a balance of the magnitudes of these immune responses determines susceptibility versus resistance to HBV (Tables 1A and 1B).…”

In vivo proliferation of hepadnavirus-infected hepatocytes induces loss of covalently closed circular DNA in mice

“…Further studies are needed to investigate whether stability of the cccDNA is similarly affected in HBV-infected human hepatocytes repopulating the uPA mouse livers and whether specific factors present in the milieu of liver regeneration can directly suppress viral replication in vivo. 23,24 We considered the possibility that part of the intrahepatic viral DNA detected toward the end of the study may have originated from integrations promoted in the course of hepatocyte turnover, as has been shown in cell culture and in the woodchuck system. 9,18,25 However, viral integrations did not accumulate in chronically infected tupaia hepatocytes serially transplanted into uPA mice.…”

Multiple cytokine expression profiles reveal immune-based differences in occult hepatitis B genotype H-infected Mexican Nahua patients

“…2. High IL-6 levels are associated with a reduction in HBV replication and IL-1 is important in many inflammatory processes associated with HBV infection, including HCC (Hirankarn et al 2006, Kuo et al 2009). However, IL-1 and IL-6 levels were undetectable in the study groups.…”