Antiviral effect of human recombinant interleukin-12 in patients infected with hepatitis C virus

✍ Scribed by Lee, Jung-Hun; Teuber, Gerlinde; von Wagner, Michael; Roth, Willi Kurt; Zeuzem, Stefan

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 293 KB
• Volume: 60
• Category: Article
• ISSN: 0146-6615
• DOI: 10.1002/(sici)1096-9071(200003)60:3<264::aid-jmv3>3.0.co;2-j

✦ Synopsis

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-␣ 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-␣ nonresponders 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 × 10 6 copies/mL) showed no significant changes during IL-12 treatment (57.3 ± 58.8 U/L and 3.2 × 10 6 copies/mL, 50.3 ± 46.2 U/L and 3.1 × 10 6 copies/mL, and 46.8 ± 35.3 U/L and 3.9 × 10 6 copies/mL at weeks 1, 4, and 10, respectively). Similar results were observed in 14 IFN-␣ 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-␣, 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.