INDUCTION OF INTERLEUKIN-12 PRODUCTION IN CHRONIC HEPATITIS-C VIRUS-INFECTION CORRELATES WITH THE HEPATOCELLULAR DAMAGE

Interleukin (IL)-12 plays an essential role in host defense against in fectious diseases. Serum IL-12 concentration and blood mononuclear cel l production with or without specific interferon (IFN)-gamma priming w ere investigated in 65 chronic hepatitis C virus (HCV) patients and 25 healthy donors. HCV patients had higher serum IL-12 levels (P = .004) and produced higher amounts after IFN-gamma priming (P < .001) than d onors. A subset of patients did not produce IL-12: They had lower seru m levels (P = .032) and showed signs of liver piecemeal necrosis less frequently (P = .011). Patients with greater liver necroinflammatory a ctivity produced more IL-12 than patients with minimal or mild activit y and donors (P < .01). During IFN-alpha therapy for 16 HCV patients, individuals with end-of-treatment alanine aminotransferase normalizati on and clearance of viremia had higher serum levels and produced more IL-12 than those who did not (P < .05). These results suggest a role f or IL-12 in the immunopathogenesis and outcome of HCV infection.