Normal volunteers received single doses of recombinant human interleukin-10 (rhIL-10; n = 6 per group) or placebo (n = 3 per group) by intravenous injection to characterize pharmacokinetics, tolerability, and immunomodulatory effects. Dosages were 0.1, 0.5, 1.0, 2.5, 5.0, 10.0, 25.0, 50.0, and 100.0 micrograms/kg. Dose-related adverse effects consisted of a mild-to-moderate flu-like syndrome characterized by fever with chills, headache, and myalgias at the highest dose. The mean terminal phase t1/2 ranged from 2.3 +/- 0.5 to 3.7 +/- 0.8 hours. Dose-related effects of rhIL-10 included transient increases of circulating neutrophils and monocytes and decreases of lymphocytes. rhIL-10 markedly suppressed, in a time- and dose-dependent manner, the synthesis of the inflammatory cytokines IL-1 beta and tumor necrosis factor alpha by whole blood stimulated ex vivo with bacterial lipopolysaccharide. Circulating numbers of CD14+/HLA-DR+ cells at 24 hours after the dose were increased in a dose-dependent manner. Effects on expression of HLA-DR by CD14+ cells were variable. There was no apparent effect on HLA-DR expression by CD20+ cells. The immunomodulatory effects of rhIL-10 merit further clinical investigation.
ARTICLES|
January 15, 1996
Pharmacokinetics and immunomodulatory properties of intravenously administered recombinant human interleukin-10 in healthy volunteers
RD Huhn,
RD Huhn
Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903–0019, USA.
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E Radwanski,
E Radwanski
Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903–0019, USA.
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SM O'Connell,
SM O'Connell
Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903–0019, USA.
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MG Sturgill,
MG Sturgill
Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903–0019, USA.
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L Clarke,
L Clarke
Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903–0019, USA.
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RP Cody,
RP Cody
Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903–0019, USA.
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MB Affrime,
MB Affrime
Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903–0019, USA.
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DL Cutler
DL Cutler
Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903–0019, USA.
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Blood (1996) 87 (2): 699–705.
Citation
RD Huhn, E Radwanski, SM O'Connell, MG Sturgill, L Clarke, RP Cody, MB Affrime, DL Cutler; Pharmacokinetics and immunomodulatory properties of intravenously administered recombinant human interleukin-10 in healthy volunteers. Blood 1996; 87 (2): 699–705. doi: https://doi.org/10.1182/blood.V87.2.699.bloodjournal872699
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