The novel strategy to treat chronic WHV hepatitis is based on adenovirus-mediated delivery of murine IL-12 (mIL-12) gene into hepatocytes [166] . Interleukin-12 is a proinflammatory cytokine produced naturally by antigen presenting cells. IL-12 stimulates production of IFNγ and TNFα by T and natural killer (NK) cells and enhances their cytotoxic activity [174] . In the study, mIL-12 gene expression could be regulated by inducible promoter that was responding to progesterone antagonist RU486. Eight chronic WHV carriers received single dose of 2 × 10 10 i.u. of AdV expressing mIL-12 (HC-Ad/RUmIL-12) by intrahepatic injection at laparotomy. Two weeks after, the expression of mIL-12 was induced by the administration of RU486. The IL-12 treatment resulted in intense and sustained suppression of WHV replication in the liver as well as decreased viral loads in the serum. This effect, however, was visible only in the animals with basal viremia lower than 10 10 WHV copies per milliliter of serum. Animals, which responded to the therapy, developed a vigorous T cell response to WHcAg, measured by woodchuck IL-2 production, and demonstrated WHeAg and WHsAg seroconversion. Moreover, the FoxP3 levels in the livers of those animals were decreased, while in nonresponder woodchucks FoxP3 values were significantly upregulated [166] . This finding suggests that the intrahepatic expression of IL-12 may inhibit the regulatory T cells in the liver during the chronic WHV infection. Indirect induction of inflammatory cytokines, such as IFNγ and TNFα by IL-12, seems to be a more efficient strategy in breaking the tolerance to virus antigens than direct delivery of those cytokines. It suggests that probably additional events occur in the liver after AdV-mediated IL-12 transfer that supports the antiviral effects of this therapy.