In vitro, IL-10 inhibits T cell proliferation and LPS-induced monocyte production of IL-1, TNF-alpha, IL-6, and IL-8. We studied the safety and immunomodulatory effects of IL-10 administration in humans. Seventeen healthy volunteers received a single i.v. bolus injection of either human IL-10 (1, 10, or 25 micrograms/kg) or placebo. Routine safety parameters, lymphocyte phenotypes, T cell proliferative responses, and stimulus-induced cytokine production were assessed before and 3, 6, 24, and 48 h after injection. There were no adverse symptoms or signs after IL-10 administration. A transient neutrophilia and monocytosis that peaked at 6 h (45-160% above base line) was observed. However, lymphocyte counts fell by 25% 3 and 6 h after the injection (p < 0.01). In particular, lymphocytes expressing the T cell surface markers CD2, CD3, CD4, CD7, and CD8 were significantly decreased. Mitogen-induced T cell proliferation was suppressed by up to 50% (p < 0.01) in the two higher dose groups. Significant dose-dependent inhibition (65-95%) of TNF-alpha and IL-1 beta production from whole blood stimulated ex vivo with endotoxin occurred after each dose of IL-10. In contrast, there was no reduction in the production of their respective antagonists, TNF soluble receptor p55 or IL-1 receptor antagonist. We conclude that a single intravenous injection of IL-10 is safe in humans, has inhibitory effects on T cells, and suppresses production of the pro-inflammatory cytokines TNF-alpha and IL-1 beta.