Pharmacodynamics of subcutaneous recombinant human interleukin-10 in healthy volunteers

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 mu g/kg) or placebo by subcutaneous injection (randomized double-blind assignment), Clinical adverse events were infrequent at doses below 50 mu g/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.