Interleukin-12 in the treatment of chronic hepatitis B and C.
Interleukin-12 plays a central role in mounting an effective cellular immune response directed towards elimination of intracellular pathogens. In two open label, multicenter, dose-escalation phase I/II studies tolerability, pharmacokinetics, pharmacodynamics, and efficacy of subcutaneously administered recombinant human interleukin-12 (rHuIL-12) was assessed in the treatment of chronic hepatitis B and C. Forty-six patients with chronic hepatitis B and 60 patients with chronic hepatitis C were treated for 12 and 10 consecutive weeks, respectively. rHuIL-12 was generally well tolerated, but was associated with temporary decreases in neutrophils and lymphocyte counts, and with elevations in serum transaminases and bilirubin. Serum IL-12 levels observed were higher at 0.5 microg/kg compared with 0.25 microg/kg doses, suggesting a dose-related increase in systemic exposure of IL-12. Measurable levels of interferon-gamma were also observed at the highest dose of 0.5 microg/kg. At the end of treatment HBV DNA clearance was greater in patients treated with 0.50 microg/kg (25%) or with 0.25 microg/kg (13%) compared with those given 0.03 microg/kg. In patients with chronic hepatitis C, HCV RNA remained detectable in all patients. A more than 50% decrease in pretreatment HCV RNA levels was observed in 3/16 patients (0.03 microg/kg), in 3/14 (0.10 microg/kg), in 6/15 (0.25 microg/kg), and in 8/15 patients of the 0.5 microg/kg dose group. In conclusion, antiviral activity of rHuIL-12 in patients with chronic hepatitis B or C does not appear to be advantageous in comparison to other currently available treatments.
Zeuzem
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Medizinische Klinik II, Zentrum der Inneren Medizin, Klinikum der Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. zeuzem@em.uni-frankfurt.de
Carreño
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D000293:Adolescent; D000328:Adult; D005260:Female; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use
D011994:Recombinant Proteins; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma