Immunopathogenesis of hepatitis C viral infection: Th1/Th2 responses and the role of cytokines

Hepatitis C virus is a common cause of hepatocellular injury that is associated with complex and vigorous immunologic mechanisms. Both humoral and cell-mediated immune responses participate in the host defense against hepatitis C viral infection, but there is increasing recognition of the roles played by the cell-mediated response, and in particular the cytokine system, in the immunopathogenesis of chronic hepatitis C. The cell-mediated response depends on cytotoxic and helper T-cell activity, and functions through the actions of cytokines to regulate macrophages, natural killer cells, and antiviral cellular proteins. Cytokines produced in the liver are essential in defending the host against hepatitis C invasion, but they have also been implicated in the hepatocellular injury seen in the majority of chronically infected patients. Cytokines are thought to be involved in the pathogenesis of hepatitis C under conditions where the virus can mutate effectively and evade T-cell immune defense mechanisms. Persistent infection upsets the balance between immunostimulatory and inhibitory cytokines which can prolong inflammation and lead to necrosis, fibrosis, and chronic liver disease.