SPONTANEOUS AND INDUCIBLE CYTOKINE RESPONSES IN HEALTHY HUMANS RECEIVING A SINGLE-DOSE OF IFN-ALPHA-2B - INCREASED PRODUCTION OF INTERLEUKIN-1 RECEPTOR ANTAGONIST AND SUPPRESSION OF IL-1-INDUCED IL-8

The present study was to determine whether the administration of a sin gle dose of interferon-alpha 2B (IFN-alpha 2B) to healthy humans affec ts endogenous (or basal level) or inducible cytokines in a whole blood , ex vivo culture. Twenty-four healthy volunteers received an s.c. inj ection of IFN-alpha 2b (3 x 10(6) U), and 4 volunteers received the ve hicle 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-1 beta (IL-1 beta). After 24 hs, the plasma was assayed for tumor necrosis factor-alpha ( TNF-alpha), IFN-gamma, IL-1 beta, IL-1 receptor antagonist (IL-1Ra), a nd IL-8, Treatment with IFN-alpha 2b was associated with a 4.8-fold in crease in the endogenous production of IL-1Ra in cultured blood sustai ned over 24 hs, In contrast, no change in endogenous IL-1Ra production was detected in the controls. A significant suppression (75%, p < 0.0 01) of IL-1 beta-induced IL-8 production 3 and 6 h after IFN-alpha 2b compared with control subjects was observed. These effects were also o bserved when IFN-alpha 2b was added directly to whole blood cultures i n vitro. In contrast to IL-1 stimulation, LPS stimulation of blood fro m IFN-alpha 2b-treated subjects resulted in enhanced IL-1 beta and TNF -alpha production. These results suggest that a single dose of IFN-alp ha 2b induces an anti-inflammatory state for endogenous stimuli but a proinflammatory state for exogenous endotoxin.