Pharmacokinetics and immunomodulatory properties of intravenously administered recombinant human interleukin-10 in healthy volunteers

Richard D. Huhn, Elaine Radwanski, Sean M. O'Connell, Marc Sturgill, Laura Clarke, Ronald P. Cody, Melton B. Affrime, David L. Cutler

Research output: Contribution to journalArticle

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Abstract

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 μg/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 t(1/2) 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-1β and tumor necrosis factor α 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.

Original languageEnglish (US)
Pages (from-to)699-705
Number of pages7
JournalBlood
Volume87
Issue number2
StatePublished - Jan 15 1996

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Pharmacokinetics
HLA-DR Antigens
Interleukin-10
Healthy Volunteers
Chills
Lymphocytes
Myalgia
Interleukin-1
Intravenous Injections
Headache
Lipopolysaccharides
Monocytes
Neutrophils
Blood
Fever
Tumor Necrosis Factor-alpha
Placebos
Cytokines

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Huhn, R. D., Radwanski, E., O'Connell, S. M., Sturgill, M., Clarke, L., Cody, R. P., ... Cutler, D. L. (1996). Pharmacokinetics and immunomodulatory properties of intravenously administered recombinant human interleukin-10 in healthy volunteers. Blood, 87(2), 699-705.
Huhn, Richard D. ; Radwanski, Elaine ; O'Connell, Sean M. ; Sturgill, Marc ; Clarke, Laura ; Cody, Ronald P. ; Affrime, Melton B. ; Cutler, David L. / Pharmacokinetics and immunomodulatory properties of intravenously administered recombinant human interleukin-10 in healthy volunteers. In: Blood. 1996 ; Vol. 87, No. 2. pp. 699-705.
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abstract = "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 μg/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 t(1/2) 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-1β and tumor necrosis factor α 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.",
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Huhn, RD, Radwanski, E, O'Connell, SM, Sturgill, M, Clarke, L, Cody, RP, Affrime, MB & Cutler, DL 1996, 'Pharmacokinetics and immunomodulatory properties of intravenously administered recombinant human interleukin-10 in healthy volunteers', Blood, vol. 87, no. 2, pp. 699-705.

Pharmacokinetics and immunomodulatory properties of intravenously administered recombinant human interleukin-10 in healthy volunteers. / Huhn, Richard D.; Radwanski, Elaine; O'Connell, Sean M.; Sturgill, Marc; Clarke, Laura; Cody, Ronald P.; Affrime, Melton B.; Cutler, David L.

In: Blood, Vol. 87, No. 2, 15.01.1996, p. 699-705.

Research output: Contribution to journalArticle

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AU - Huhn, Richard D.

AU - Radwanski, Elaine

AU - O'Connell, Sean M.

AU - Sturgill, Marc

AU - Clarke, Laura

AU - Cody, Ronald P.

AU - Affrime, Melton B.

AU - Cutler, David L.

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N2 - 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 μg/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 t(1/2) 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-1β and tumor necrosis factor α 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.

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