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 language||English (US)|
|Number of pages||7|
|State||Published - Jan 15 1996|
All Science Journal Classification (ASJC) codes
- Cell Biology