PHARMACOKINETICS AND IMMUNOMODULATORY PROPERTIES OF INTRAVENOUSLY ADMINISTERED RECOMBINANT HUMAN INTERLEUKIN-10 IN HEALTHY-VOLUNTEERS

Normal volunteers received single doses of recombinant human interleuk in-10 (rhIL-10; n = 6 per group) or placebo (N = 3 per group) by intra venous injection to characterize pharmacokinetics, tolerability, and i mmunomodulatory effects. Dosages were 0.1, 0.5, 1.0, 2.5, 5.0, 10.0, 2 5.0, 50.0, and 100.0 mu g/kg Dose-related adverse effects consisted of a mild-to-moderate flu-like syndrome characterized by fever with chil ls, headache, and myalgias at the highest dose. The mean terminal phas e t(1/2) ranged from 2.3 +/- 0.5 to 3.7 +/- 0.8 hours. Dose-related ef fects of rhIL-10 included transient increases of circulating neutrophi ls and monocytes and decreases of lymphocytes. rhIL-10 markedly suppre ssed, in a time- and dose-dependent manner, the synthesis of the infla mmatory cytokines IL-1 beta and tumor necrosis factor alpha by whole b lood stimulated ex vivo with bacterial lipopolysaccharide. Circulating numbers of CD14(+)/HLA-DR(+) cells at 24 hours after the dose were in creased in a dose-dependent manner. Effects on expression of HLA-DR by CD14(+) cells were variable. There was no apparent effect on HLA-DR e xpression by CD20(+) cells. The immunomodulatory effects of rhIL-10 me rit further clinical investigation. (C) 1996 by The American Society o f Hematology.