title: A randomized, controlled trial of IL-10 in humans. Inhibition of inflammatory cytokine production and immune responses.
abstract: 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.
authors.affiliation: Department of Medicine, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Chernoff
authors.forename: E V
authors.initials: EV
authors.lastname: Granowitz
authors.forename: L
authors.initials: L
authors.lastname: Shapiro
authors.forename: E
authors.initials: E
authors.lastname: Vannier
authors.forename: G
authors.initials: G
authors.lastname: Lonnemann
authors.forename: J B
authors.initials: JB
authors.lastname: Angel
authors.forename: J S
authors.initials: JS
authors.lastname: Kennedy
authors.forename: A R
authors.initials: AR
authors.lastname: Rabson
authors.forename: S M
authors.initials: SM
authors.lastname: Wolff
authors.forename: C A
authors.initials: CA
authors.lastname: Dinarello
mesh_terms: D000293:Adolescent; D000328:Adult; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D004311:Double-Blind Method; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007275:Injections, Intravenous; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000008:administration & dosage / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000187:drug effects; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D010835:Phytohemagglutinins; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10