A RANDOMIZED, CONTROLLED TRIAL OF IL-10 IN HUMANS - INHIBITION OF INFLAMMATORY CYTOKINE PRODUCTION AND IMMUNE-RESPONSES

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. Sevent een healthy volunteers received a single i.v. bolus injection of eithe r human IL-10 (7, 10, or 25 mu g/kg) or placebo. Routine safety parame ters, lymphocyte phenotypes, T cell proliferative responses, and stimu lus-induced cytokine production were assessed before and 3, 6, 24, and 48 h after injection. There were no adverse symptoms or signs after I L-10 administration. A transient neutrophilia and monocytosis that pea ked 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 parti cular, lymphocytes expressing the T cell surface markers CD2, CD3, CD4 , CD7, and CD8 were significantly decreased. Mitogen-induced T cell pr oliferation was suppressed by up to 50% (p < 0.01) in the two higher d ose groups. Significant dose-dependent inhibition (65-95%) of TNF-alph a and IL-1 beta production from whole blood stimulated ex vivo with en dotoxin occurred after each dose of IL-10. In contrast, there was no r eduction in the production of their respective antagonists, TNF solubl e receptor p55 or IL-1 receptor antagonist. We conclude that a single intravenous injection of IL-10 is safe in humans, has inhibitory effec ts on T cells, and suppresses production of the pro-inflammatory cytok ines TNF-alpha and IL-1 beta.