Purified human interleukin-2 enhances induction of immune interferon

Abstract

Interleukin-2 (IL-2), purified to apparent homogeneity, enhanced interferon (IFN) production in phytohemagglutin (PHA)-stimulated cultures of Ficoll-Hypaque-purified human mononuclear cells derived from plateletpheresis residues. Cells incubated with IL-2 in the absence of PHA did not produce detectable IFN. Neutralization with specific antisera and lack of activity in bovine cells indicated that the IFN produced in cells treated with IL-2 was IFN gamma. Addition of IL-2 to cultures stimulated IFN production in a dose-dependent fashion, with 100 U/ml of IL-2 generally producing optimal stimulation. There was considerable variability in the magnitude of the IFN response and the degree of its enhancement by IL-2 treatment in cells from different donors. However, an enhancement of IFN production after treatment with 100 U/ml of IL-2 was regularly observed in 11 experiments, with the increase ranging from 3- to 37-fold (mean 8.6-fold). The difference between IFN yields in control cultures and cultures treated with 100 U/ml of IL-2 was statistically significant (P less than 0.001). In contrast, 1000 U/ml of IL-2 strongly inhibited IFN induction by PHA. Treatment of cultures with IL-2 did not alter the kinetics of IFN production which peaked at 48-72 hr after PHA stimulation. When PHA was added only 24 to 96 hr after the establishment of cultures, rather than at the time of their seeding, both IFN production and endogenous IL-2 production were enhanced. The addition of exogenous IL-2 to such cultures caused only a modest further enhancement of IFN production. These data suggest that a threshold concentration of IL-2 (exogenously added or endogenously produced) is required for optimal IFN gamma production by human mononuclear cells.