Effects of recombinant human leukocyte interferon treatment of endogenous interferon production in patients with chronic type-B hepatitis.

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 (alpha) IFN (IFN-alpha) ranging from 5 X 10(6) units daily to 60 X 10(6) thrice weekly. The production of endogenous IFN stimulated by specific inducers (Sendai virus for IFN-alpha; phytohemagglutinin for IFN-gamma) 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-alpha was noted after 2 weeks. Priming of endogenous IFN-alpha production, as reflected by earlier production of IFN by PBMCs in culture, occurred in all treated patients irrespective of the dose of IFN-alpha received. Whereas mean 24-hour (total) endogenous IFN-alpha 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-alpha 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-alpha production, IFN-gamma production by PBMCs was not affected by IFN-alpha treatment.(ABSTRACT TRUNCATED AT 250 WORDS)