Key result
Recombinant human interleukin-12 induced changes in HCV quasispecies in 83% of patients compared to 21% of untreated controls (P<0.003), but did not significantly reduce serum HCV RNA levels.
Why the study?
Does recombinant human IL-12 reduce hepatitis C viremia and alter quasispecies in patients who are non-responders to IFN-alpha?
Does recombinant human IL-12 reduce hepatitis C viremia and alter quasispecies in patients who are non-responders to IFN-alpha?
Interleukin-12 exerts only limited antiviral activity against certain HCV quasispecies in vivo without significantly reducing overall viral load or ALT levels.
Answers are grounded in this paper and cite their sources.
IL-12 alters HCV quasispecies without reducing viremia; hypothesis-generating for selective antiviral effects in IFN-nonresponders.
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-alpha treatment, received recombinant human IL-12 s.c. once weekly for 10 weeks stratified to three dose schedules (0.03 microg/kg, 0.1 microg/kg, and 0.5 microg/kg body weight, respectively). Fourteen IFN-alpha 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 x 10(6) copies/mL) showed no significant changes during IL-12 treatment (57.3 +/- 58.8 U/L and 3.2 x 10(6) copies/mL, 50.3 +/- 46.2 U/L and 3.1 x 10(6) copies/mL, and 46.8 +/- 35.3 U/L and 3.9 x 10(6) copies/mL at weeks 1, 4, and 10, respectively). Similar results were observed in 14 IFN-alpha 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-alpha, 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.
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Lee et al. (2000) studied Hepatitis C virus infection (n=40). Recombinant human interleukin-12 vs. Untreated patients and IFN-alpha non-responders was evaluated on Changes in HCV quasispecies (p=< 0.003). Recombinant human interleukin-12 induced changes in HCV quasispecies in 83% of patients compared to 21% of untreated controls (P<0.003), but did not significantly reduce serum HCV RNA levels.
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