title: Spontaneous and inducible cytokine responses in healthy humans receiving a single dose of IFN-alpha2b: 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-alpha2B (IFN-alpha2B) 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-alpha2b (3 x 10(6)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-1beta (IL-1beta). After 24 hs, the plasma was assayed for tumor necrosis factor-alpha (TNF-alpha), IFN-gamma, IL-1beta, IL-1 receptor antagonist (IL-1Ra), and IL-8. Treatment with IFN-alpha2b was associated with a 4.8-fold increase in the endogenous production of IL-1Ra 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-1beta-induced IL-8 production 3 and 6 h after IFN-alpha2b compared with control subjects was observed. These effects were also observed when IFN-alpha2b was added directly to whole blood cultures in vitro. In contrast to IL-1 stimulation, LPS stimulation of blood from IFN-alpha2b-treated subjects resulted in enhanced IL-1beta and TNF-alpha production. These results suggest that a single dose of IFN-alpha2b induces an anti-inflammatory state for endogenous stimuli but a proinflammatory state for exogenous endotoxin.
authors.affiliation: Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
authors.forename: L L
authors.initials: LL
authors.lastname: Reznikov
authors.forename: A J
authors.initials: AJ
authors.lastname: Puren
authors.forename: G
authors.initials: G
authors.lastname: Fantuzzi
authors.forename: H
authors.initials: H
authors.lastname: Mühl
authors.forename: L
authors.initials: L
authors.lastname: Shapiro
authors.forename: D Y
authors.initials: DY
authors.lastname: Yoon
authors.forename: D L
authors.initials: DL
authors.lastname: Cutler
authors.forename: C A
authors.initials: CA
authors.lastname: Dinarello
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D016207:Cytokines / Q000096:biosynthesis*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins; D012016:Reference Values
chemical_list: D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007375:Interleukin-1; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins