title: Pharmacodynamics of subcutaneous recombinant human interleukin-10 in healthy volunteers.
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.
authors.affiliation: Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Huhn
authors.forename: E
authors.initials: E
authors.lastname: Radwanski
authors.forename: J
authors.initials: J
authors.lastname: Gallo
authors.forename: M B
authors.initials: MB
authors.lastname: Affrime
authors.forename: R
authors.initials: R
authors.lastname: Sabo
authors.forename: G
authors.initials: G
authors.lastname: Gonyo
authors.forename: A
authors.initials: A
authors.lastname: Monge
authors.forename: D L
authors.initials: DL
authors.lastname: Cutler
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D004311:Double-Blind Method; D004926:Escherichia coli; D005260:Female; D006207:Half-Life; D006801:Humans; D007279:Injections, Subcutaneous; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D012449:Safety; D012795:Sialoglycoproteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10