Pharmacodynamics of subcutaneous recombinant human interleukin-10 in healthy volunteers

Clin Pharmacol Ther. 1997 Aug;62(2):171-80. doi: 10.1016/S0009-9236(97)90065-5.

Abstract

Interleukin-10 inhibits T-lymphocyte activation and proliferation and lipopolysaccharide-induced monocyte production of proinflammatory cytokines. Fifty-four healthy volunteers received single doses of recombinant human interleukin-10 (1.0, 2.5, 5.0, 10, 25, or 50 micrograms/kg) or placebo by subcutaneous injection (randomized double-blind assignment). Clinical adverse events were infrequent at doses below 50 micrograms/kg (five of six subjects had mild flu-like syndrome). Mean serum interleukin-10 concentrations were dose related. The mean terminal-phase half-life ranged from 2.7 to 4.5 hours, and the apparent volume of distribution ranged from 0.70 to 1.35 L/kg. Hematologic changes included transient mild to moderate increases of neutrophil counts, decreases of lymphocyte counts, and a delayed decrease of platelet counts. Recombinant human interleukin-10 significantly suppressed production of the proinflammatory cytokines interleukin-1 beta and tumor necrosis factor-alpha by whole blood stimulated ex vivo with Escherichia coli lipopolysaccharide.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / metabolism
  • Double-Blind Method
  • Escherichia coli
  • Female
  • Half-Life
  • Humans
  • Injections, Subcutaneous
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / metabolism
  • Interleukin-10 / adverse effects
  • Interleukin-10 / pharmacokinetics
  • Interleukin-10 / pharmacology*
  • Lipopolysaccharides / pharmacology
  • Lymphocyte Activation / drug effects*
  • Male
  • Receptors, Interleukin-1 / metabolism
  • Receptors, Tumor Necrosis Factor / metabolism
  • Receptors, Tumor Necrosis Factor, Type I
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / pharmacokinetics
  • Recombinant Proteins / pharmacology*
  • Safety
  • Sialoglycoproteins / metabolism
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antigens, CD
  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Lipopolysaccharides
  • Receptors, Interleukin-1
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Recombinant Proteins
  • Sialoglycoproteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-10