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RESEARCH PRODUCT

Pilot study of natural human interleukin-2 in patients with chronic hepatitis B

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description

Ten patients with chronic hepatitis B received increasing doses of nIL-2 (30 000 U, 100 000 U, 300 000 U, 1.0 million U) subcutaneously in a phase I trial. Each dose was applied once per week over 3 weeks. Serum samples were taken before and 2, 12, 24, 48 and 72 h after the first application of each dose level. Serum concentrations of interleukin-1 (IL-1), IL-2, IL-6, interferon-alfa (IFN- α ), IFN- γ , tumor necrosis factor- α (TNF- α ) and GM-CSF as well as the cytokine-dependent serum components neopterin, beta-2-microglobulin (B2M), C-reactive protein (CPR), soluble IL-2-receptor (sIL-2R) and 2′-5′-oligoadenylate synthetase (2–5 OA) were assayed using ELISAs and RIAs. None of the samples tested contained measurable cytokine levels other than IL-2. A low and non-toxic dose of 300 000 U nIL-2 was already biologically active with induction of neopterin, B2M and sIL-2R. Dose-dependent changes peaked 24–48 h after application. The same patients were then enrolled in a phase II trial. Treatment in five of the patients was continued twice per week for 3 months with a biologically active dose of 300 000 U nIL-2 subcutaneously. Two of these patients as well as another five patients from the original group were treated with 1.0 million U nIL-2 subcutaneously, twice weekly for 3 months. Neither a biologically active but non-toxic dose of 300 000 U nIL-2, nor a toxic dose of 1.0 million U resulted in permanent clearance of hepatitis B early antigen (HBeAg). However, after dose escalation there was more than 50% reduction in serum hepatitis B virus (HBV) DNA in 4/7 patients. This reduction was accompanied by a flare of hepatitis. These results indicate that low and non-toxic doses of nIL-2 give immunomodulatory features in patients with chronic hepatitis B. Antiviral effects were only observed with higher and toxic doses.