Clinical, hematologic, and immunologic effects of interleukin-10 in humans.
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.
Fuchs
A C
AC
Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts, USA.
Granowitz
E V
EV
Shapiro
L
L
Vannier
E
E
Lonnemann
G
G
Angel
J B
JB
Kennedy
J S
JS
Rabson
A R
AR
Radwanski
E
E
Affrime
M B
MB
Cutler
D L
DL
Grint
P C
PC
Dinarello
C A
CA
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
D015850:Interleukin-6; D016209:Interleukin-8; D013481:Superoxides; D016753:Interleukin-10; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor