Spontaneous and Inducible Cytokine Responses in Healthy Humans Receiving a Single Dose of IFN-α2b: Increased Production of Interleukin-1 Receptor Antagonist and Suppression of IL-1-Induced IL-8

Abstract

The present study was to determine whether the administration of a single dose of interferon-α2B (IFN-α2B) to healthy humans affects endogenous (or basal level) or inducible cytokines in a whole blood, ex vivo culture. Twenty-four healthy volunteers received an s.c. injection of IFN-α2b (3 × 10⁶ U), and 4 volunteers received the vehicle as placebo. The study was blinded. Blood was drawn before and 3, 6, 12, and 24 h after the injection and incubated in the presence or absence of lipopolysaccharide (LPS) or interleukin-Iβ (IL-1β). After 24 hs, the plasma was assayed for tumor necrosis factor-α (TNF-α), IFN-γ, IL-1β, IL-1 receptor antagonist (IL-IRa), and IL-8. Treatment with IFN-α2b was associated with a 4.8-fold increase in the endogenous production of IL-IRa in cultured blood sustained over 24 hs. In contrast, no change in endogenous IL-1Ra production was detected in the controls. A significant suppression (75%, p < 0.001) of IL-1β-induced IL-8 production 3 and 6 h after IFN-α2b compared with control subjects was observed. These effects were also observed when IFN-α2b was added directly to whole blood cultures in vitro. In contrast to IL-1 stimulation, LPS stimulation of blood from IFN-α2b-treated subjects resulted in enhanced IL-1β and TNF-α production. These results suggest that a single dose of IFN-α2b induces an anti-inflammatory state for endogenous stimuli but a proinflammatory state for exogenous endotoxin.