title: Pharmacokinetics and immunomodulatory properties of intravenously administered recombinant human interleukin-10 in healthy volunteers.
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 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.
authors.affiliation: Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903-0019, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Huhn
authors.forename: E
authors.initials: E
authors.lastname: Radwanski
authors.forename: S M
authors.initials: SM
authors.lastname: O'Connell
authors.forename: M G
authors.initials: MG
authors.lastname: Sturgill
authors.forename: L
authors.initials: L
authors.lastname: Clarke
authors.forename: R P
authors.initials: RP
authors.lastname: Cody
authors.forename: M B
authors.initials: MB
authors.lastname: Affrime
authors.forename: D L
authors.initials: DL
authors.lastname: Cutler
mesh_terms: D000293:Adolescent; D000328:Adult; D016207:Cytokines / Q000378:metabolism*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007155:Immunologic Factors; D007275:Injections, Intravenous; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D007958:Leukocyte Count / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010146:Pain / Q000139:chemically induced; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D006684:HLA-DR Antigens; D007155:Immunologic Factors; D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10