PILOT-STUDY OF NATURAL HUMAN INTERLEUKIN-2 IN PATIENTS WITH CHRONIC HEPATITIS-B - IMMUNOMODULATORY AND ANTIVIRAL EFFECTS

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. Seru m samples were taken before and 2, 12, 24, 48 and 72 h after the first application of each dose lever. Serum concentrations of interleukin-1 (IL-1), IL-2, IL-6, interferon-alfa (IFN-alpha), IFN-gamma, tumor nec rosis factor-alpha (TNF-alpha) and GM-CSF as well as the cytokine-depe ndent serum components neopterin, beta-2-microglobulin (B2M) C-reactiv e protein (CPR), soluble IL-2-receptor (sIL-2R) and 2'-5'-oligoadenyla te 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 a ctive with induction of neopterin, B2M and sIL-2R. Dose-dependent chan ges peaked 24-48 h after application. The same patients were then enro lled in a phase II trial. Treatment in five of the patients was contin ued 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 biologicall y 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 antig en (HBeAg). However, after dose escalation there was more than 50% red uction in serum hepatitis B virus (HBV) DNA in 4/7 patients. This redu ction was accompanied by a flare of hepatitis. These results indicate that low and non-toxic doses of nIL-2 give immunomodulatory features i n patients with chronic hepatitis B. Antiviral effects were only obser ved with higher and toxic doses.