Effects of Recombinant Human Leukocyte Interferon Treatment on Endogenous Interferon Production in Patients with Chronic Type-B Hepatitis

Abstract

Interferon (IFN) added to cell culture systems alters the capacity of the cells to produce IFN when appropriately stimulated. To evaluate the effects of in vivo administration of IFN on the production of IFN by peripheral blood mononuclear cells (PBMCs), we studied patients with chronic type-B hepatitis who received doses of recombinant human leukocyte (α) IFN (IFN-α) ranging from 5 × 10⁶ units daily to 60 × 106 thrice weekly. The production of endogenous IFN stimulated by specific inducers (Sendai virus for IFN-α; phytohemagglutinin for IFN-γ) was studied in cell cultures containing PBMCs obtained from patients before or during courses of IFN treatment. In untreated controls, no change in the mean capacity of PBMCs to produce IFN-α was noted after 2 weeks. Priming of endogenous IFN-α production, as reflected by earlier production of IFN by PBMCs in culture, occurred in all treated patients irrespective of the dose of IFN-α received. Whereas mean 24-hour (total) endogenous IFN-α fell in all treatment groups, the response was highly variable in individual patients and half showed no change in total production. Individual variations in endogenous IFN-α production were unrelated to serum IFN levels achieved during treatment, changes in serum aminotransferase levels, reduction of hepatitis B virus replication during therapy, or the proportions of T and B lymphocytes in culture. In contrast to the changes in IFN-α production, IFN-γ production by PBMCs was not affected by IFN-α treatment. These findings suggest that while exogenous IFN-α primes endogenous production of IFN-α, it is unlikely to have a significant effect on the capacity of PBMCs to produce IFN in the majority of patients.