Decreased interferon binding capacity of peripheral blood mononuclear cells during interferon treatment of chronic hepatitis B with special reference to (2′-5′) oligoadenylate synthetase activity

Abstract

The levels of (2'-5') oligoadenylate synthetase (2-5 AS) activity and interferon (IFN) binding capacity were measured in peripheral blood mononuclear cells (PBMC) obtained from 9 patients with chronic hepatitis B (CHB) during IFN treatment. Six of the patients received human lymphoblastoid IFN (HLBI) or IFN-beta daily for 4 weeks at doses of 6 million units (MU); of the remaining three, 2 were treated on alternate days at doses of 3 MU for 5 weeks, and the other given daily IFN doses of 3 MU for 4 weeks. IFN binding was measured using HLBI (2 X 10(8) IU/mg protein) and completely purified 125I-labeled HLBI (290 Ci/mmol specific activity). The levels of 2-5 AS activity in PBMC were measured using radioimmunoassay. Before IFN treatment, the levels of IFN binding capacity were similar to those of normal subjects. During treatment, however, IFN binding capacity decreased significantly from 40 to 60% of initial levels 1 to 2 weeks after the start of treatment in the 7 patients receiving daily IFN, while in the remaining 2 patients given IFN on alternate days, IFN binding capacity did not decrease during treatment. On the other hand, 2-5 AS activity in PBMC increased during IFN treatment in all patients. Even after IFN binding capacity decreased in the 7 patients, the levels of 2-5 AS activity remained high during the remainder of treatment. These finding suggest that some mechanism other than IFN binding capacity may be responsible for the determination of 2-5 AS levels.