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

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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.

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Authors and Affiliations

  1. Department of Medicine, Tufts University School of Medicine and the New England Medical Center, Boston, Massachusetts

    Amy C. Fuchs, Eric V. Granowitz, Leland Shapiro, Edouard Vannier, Gerhard Lonnemann, Jonathan B. Angel, Jeffrey S. Kennedy & Charles A. Dinarello

  2. Department of Pathology, Tufts University School of Medicine and the New England Medical Center, Boston, Massachusetts

    Arthur R. Rabson

  3. Schering-Plough Research Institute, Kenilworth, New Jersey

    Elaine Radwanski, Melton B. Affrime, David L. Cutler & Paul C. Grint

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  1. Amy C. Fuchs
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  2. Eric V. Granowitz
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  3. Leland Shapiro
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  4. Edouard Vannier
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  5. Gerhard Lonnemann
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  6. Jonathan B. Angel
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  7. Jeffrey S. Kennedy
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  8. Arthur R. Rabson
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  13. Charles A. Dinarello
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Fuchs, A.C., Granowitz, E.V., Shapiro, L. et al. Clinical, hematologic, and immunologic effects of interleukin-10 in humans. J Clin Immunol 16, 291–303 (1996). https://doi.org/10.1007/BF01541395

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