Antiviral effect of human recombinant interleukin-12 in patients infected with hepatitis C virusPresented in part: 49th American Association for the Study of Liver Diseases meeting, Chicago, IL, 6–10 November 1998 (abstract # 1239)

Abstract

The heterogeneity of hepatitis C virus (HCV) is due to the continuous and high replication rate, the low fidelity of the RNA-dependent RNA polymerase, and the immune surveillance of the host. Interleukin-12 (IL-12) plays a central role in mounting an effective cellular immune response directed towards elimination of intracellular pathogens. The effect of IL-12 on hepatitis C viremia and the HCV quasispecies population is unknown. In this study, 12 patients (9 males, 3 females; mean age: 44 ± 11 years), all virological non-responders to previous IFN-α treatment, received recombinant human IL-12 s.c. once weekly for 10 weeks stratified to three dose schedules (0.03 μg/kg, 0.1 μg/kg, and 0.5 μg/kg body weight, respectively). Fourteen IFN-α non-responders and 14 untreated patients served as age- and sex-matched controls. Serum HCV RNA concentrations and HCV quasispecies distribution were measured serially by quantitative reverse transcription - polymerase chain reaction and single strand conformation polymorphism analysis of the hypervariable region of the second envelope gene, respectively. Serum ALT and median HCV RNA levels before treatment (52.7 ± 21.7 U/L; 2.6 × 106 copies/mL) showed no significant changes during IL-12 treatment (57.3 ± 58.8 U/L and 3.2 × 106 copies/mL, 50.3 ± 46.2 U/L and 3.1 × 106 copies/mL, and 46.8 ± 35.3 U/L and 3.9 × 106 copies/mL at weeks 1, 4, and 10, respectively). Similar results were observed in 14 IFN-α non-responders and 14 untreated patients. However, changes in HCV quasispecies occurred in 10/12 (83%) and 9/14 (64%) patients treated with interleukin-12 and interferon-α, respectively, but only in 3/14 (21%) untreated subjects (P < 0.003 and P < 0.03). These results imply that interleukin-12 exerts only limited antiviral activity against certain HCV quasispecies in vivo. J. Med. Virol. 60:264–268, 2000. © 2000 Wiley-Liss, Inc.