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 μg/kg) or placebo by subcutaneous injection (randomized double‐blind assignment). Clinical adverse events were infrequent at doses below 50 μg/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‐1β and tumor necrosis factor‐α by whole blood stimulated ex vivo with Escherichia coli lipopolysaccharide. Clinical Pharmacology & Therapeutics (1997) 62, 171–180; doi: