Clinical, hematologic, and immunologic effects of interleukin-10 in humans

被引:75
作者
Fuchs, AC
Granowitz, EV
Shapiro, L
Vannier, E
Lonnemann, G
Angel, JB
Kennedy, JS
Rabson, AR
Radwanski, E
Affrime, MB
Cutler, DL
Grint, PC
Dinarello, CA
机构
[1] TUFTS UNIV,SCH MED,DEPT MED,BOSTON,MA 02111
[2] TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111
[3] TUFTS UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02111
[4] SCHERING PLOUGH CORP,RES INST,KENILWORTH,NJ
关键词
cytokines; interleukin-6; interleukin-8; interferon-gamma; Th1 and Th2 lymphocytes;
D O I
10.1007/BF01541395
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 mu g/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 mu g/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 mu g/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.
引用
收藏
页码:291 / 303
页数:13
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