CLINICAL, HEMATOLOGIC, AND IMMUNOLOGICAL EFFECTS OF INTERLEUKIN-10 INHUMANS

We conducted a double-blind, placebo-controlled study to investigate t he safety, pharmacokinetics, and immunological properties of interleuk in-10 (IL-10) administration in healthy humans. Volunteers received a single intravenous bolus injection of recombinant human IL-10 (1, 10, or 25 mu g/kg) or placebo. Cytokine production in whole blood and peri pheral blood mononuclear cells (PBMC) was assessed before and 3, 6, 24 , and 48 hr after the injection. Peak serum concentrations of IL-10 (1 5 +/- 1.1, 208 +/- 20.1, and 505 +/- 22.3 ng/ml) occurred after 2-5 mi n for 1, 10, and 25 mu g/kg IL-10, respectively. The terminal-phase ha lf-life was 3.18 hr. A transient leukocytosis (24-63% above baseline) was observed 6 hr after injection, which coincided with a dose-depende nt decrease (12-24%) in neutrophil superoxide generation. There was a marked inhibition (60-95%) of endotoxin-induced IL-6 production from w hole blood in each group receiving IL-10. Production of IL-8 in endoto xin-stimulated blood was reduced in the 10 mu g/kg. group. In PBMC sti mulated with phytohemagglutinin and phorbol ester, there was a decreas e (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 onl y partially associated with a decrease in the number of CD2-bearing ce lls. We conclude that IL-10 administration into humans is without sign ificant side effects, and a single injection reduces ex vivo productio n of IL-6, IL-8, and IFN gamma.