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

• Published in: Journal of medical virology Vol. 60; no. 3; pp. 264 - 268
• Main Authors: Lee, Jung-Hun, Teuber, Gerlinde, von Wagner, Michael, Roth, Willi Kurt, Zeuzem, Stefan
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.03.2000; Wiley-Liss
• Subjects: Adult; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Biological and medical sciences; Female; Hepacivirus - chemistry; Hepacivirus - drug effects; Hepacivirus - growth & development; Hepatitis C - drug therapy; Hepatitis C - virology; Hepatitis C virus; Human viral diseases; Humans; hypervariable region; Infectious diseases; Interferon Type I - therapeutic use; interleukin-12; Interleukin-12 - pharmacology; Interleukin-12 - therapeutic use; Male; Medical sciences; Middle Aged; Polymorphism, Single-Stranded Conformational; quasispecies; Recombinant Proteins - pharmacology; Recombinant Proteins - therapeutic use; Reverse Transcriptase Polymerase Chain Reaction; RNA, Viral - blood; RNA, Viral - drug effects; single strand conformation polymorphism; Viral diseases; Viral hepatitis; Viral Load; Human; Genetic variability; Alpha interferon; Viremia; Cytokine; Interleukin 12; Hypervariable region; Infection; Virus; Treatment; Viral disease; Immunotherapy; Antiviral; Flaviviridae; Hepatitis C virus; Hepacivirus; Viral load
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/(SICI)1096-9071(200003)60:3<264::AID-JMV3>3.0.CO;2-J

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.