Pharmacokinetics and immunomodulatory properties of intravenously administered recombinant human interleukin-10 in healthy volunteers
| Autor: | R D, Huhn, E, Radwanski, S M, O'Connell, M G, Sturgill, L, Clarke, R P, Cody, M B, Affrime, D L, Cutler |
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| Rok vydání: | 1996 |
| Předmět: |
Adult
Male Adolescent Dose-Response Relationship Drug Gastrointestinal Diseases Tumor Necrosis Factor-alpha Pain HLA-DR Antigens Lymphocyte Activation Recombinant Proteins Interleukin-10 Leukocyte Count Double-Blind Method Depression Chemical Injections Intravenous Cytokines Humans Immunologic Factors Lymphocytes Interleukin-1 |
| Zdroj: | Blood. 87(2) |
| ISSN: | 0006-4971 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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