Journal of Clinical Immunology

, Volume 16, Issue 5, pp 291–303 | Cite as

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

  • Amy C. Fuchs
  • Eric V. Granowitz
  • Leland Shapiro
  • Edouard Vannier
  • Gerhard Lonnemann
  • Jonathan B. Angel
  • Jeffrey S. Kennedy
  • Arthur R. Rabson
  • Elaine Radwanski
  • Melton B. Affrime
  • David L. Cutler
  • Paul C. Grint
  • Charles A. Dinarello
Original Articles

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 25μg/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 25μg/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 10μg/kg group. In PBMC stimulated with phytohemagglutinin and phorbol ester, there was a decrease (72–87%) in interferon-γ (IFNγ) 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 reducesex vivo production of IL-6, IL-8, and IFNγ.

Key words

Cytokines interleukin-6 interleukin-8 interferon-γ Th1 and Th2 lymphocytes 

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Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • Amy C. Fuchs
    • 1
  • Eric V. Granowitz
    • 1
  • Leland Shapiro
    • 1
  • Edouard Vannier
    • 1
  • Gerhard Lonnemann
    • 1
  • Jonathan B. Angel
    • 1
  • Jeffrey S. Kennedy
    • 1
  • Arthur R. Rabson
    • 2
  • Elaine Radwanski
    • 3
  • Melton B. Affrime
    • 3
  • David L. Cutler
    • 3
  • Paul C. Grint
    • 3
  • Charles A. Dinarello
    • 1
  1. 1.Department of MedicineTufts University School of Medicine and the New England Medical CenterBoston
  2. 2.Department of PathologyTufts University School of Medicine and the New England Medical CenterBoston
  3. 3.Schering-Plough Research InstituteKenilworth

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