title: Clinical, hematologic, and immunologic effects of interleukin-10 in humans.
abstract: We conducted a double-blind, placebo-controlled study to investigate the safety, pharmacokinetics, and immunological properties of interleukin-10 (IL-10) administration in healthy humans. Volunteers received a single intravenous bolus injection of recombinant human IL-10 (1, 10, or 25 micrograms/kg) or placebo. Cytokine production in whole blood and peripheral blood mononuclear cells (PBMC) was assessed before and 3, 6, 24, and 48 hr after the injection. Peak serum concentrations of IL-10 (15 +/- 1.1, 208 +/- 20.1, and 505 +/- 22.3 ng/ml) occurred after 2-5 min for 1, 10, and 25 micrograms/kg IL-10, respectively. The terminal-phase half-life was 3.18 hr. A transient leukocytosis (24-63% above baseline) was observed 6 hr after injection, which coincided with a dose-dependent decrease (12-24%) in neutrophil superoxide generation. There was a marked inhibition (60-95%) of endotoxin-induced IL-6 production from whole blood in each group receiving IL-10. Production of IL-8 in endotoxin-stimulated blood was reduced in the 10 micrograms/kg group. In PBMC stimulated with phytohemagglutinin and phorbol ester, there was a decrease (72-87%) in interferon-gamma (IFN gamma) production 6 hr after IL-10 with a return to pre-IL-10 levels after 24 hr. This reduction was only partially associated with a decrease in the number of CD2-bearing cells. We conclude that IL-10 administration into humans is without significant side effects, and a single injection reduces ex vivo production of IL-6, IL-8, and IFN gamma.
authors.affiliation: Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Fuchs
authors.forename: E V
authors.initials: EV
authors.lastname: Granowitz
authors.forename: L
authors.initials: L
authors.lastname: Shapiro
authors.forename: E
authors.initials: E
authors.lastname: Vannier
authors.forename: G
authors.initials: G
authors.lastname: Lonnemann
authors.forename: J B
authors.initials: JB
authors.lastname: Angel
authors.forename: J S
authors.initials: JS
authors.lastname: Kennedy
authors.forename: A R
authors.initials: AR
authors.lastname: Rabson
authors.forename: E
authors.initials: E
authors.lastname: Radwanski
authors.forename: M B
authors.initials: MB
authors.lastname: Affrime
authors.forename: D L
authors.initials: DL
authors.lastname: Cutler
authors.forename: P C
authors.initials: PC
authors.lastname: Grint
authors.forename: C A
authors.initials: CA
authors.lastname: Dinarello
mesh_terms: D000293:Adolescent; D000328:Adult; D000917:Antibody Formation; D001772:Blood Cell Count; D004311:Double-Blind Method; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology* / Q000493:pharmacokinetics* / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis / Q000097:blood; D008297:Male; D013481:Superoxides / Q000097:blood
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D013481:Superoxides; D016753:Interleukin-10; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor