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

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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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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., Affrime, M. B., & Cutler, D. L. (1996). Pharmacokinetics and immunomodulatory properties of intravenously administered recombinant human interleukin-10 in healthy volunteers. Blood, 87(2), 699-705.