Effects of single intravenous doses of recombinant human interleukin-10 on subsets of circulating leukocytes in humans.
Recombinant human interleukin-10 (rhIL-10) is a potent and specific immunomodulatory agent which inhibits endotoxin-stimulated pro-inflammatory cytokine production by monocytes, blocks T-lymphocyte activation by antigen presenting cells, and modulates T(H)1/T(H)2 balance in immune responses. In previous clinical trials, rhIL-10 administered to healthy volunteers induced rapid and transient elevations of neutrophil and monocyte counts and reductions of lymphocyte counts in addition to suppression of endotoxin-stimulated whole blood cytokine synthesis. We sought to better characterize the effects of rhIL-10 on immunophenotypically defined subsets of circulating leukocytes that could be relevant to its immunomodulatory effects. Healthy volunteers were given single doses of 10 microg/kg rhIL-10 (n = 8) or equivalent placebo (n = 4) by intravenous injection. Significant changes of circulating leukocytes included transiently increased neutrophils and monocytes with parallel increases of CD33+ and CD14+ cells. Total lymphocytes as well as total CD3+, CD3+/CD4+ and CD3+/CD8+ cells transiently decreased. Mean fluorescence intensity of CD11a (integrin alpha-chain subunit of lymphocyte function antigen-1, LFA-1) on lymphocytes transiently but significantly decreased, suggesting a mechanism for transient alteration of lymphocyte trafficking. In addition, mean fluorescence intensity of HLA-DR (major histocompatibility class II) on CD14+ cells (predominantly monocytes) transiently but significantly decreased, implying a possible alteration of antigen presenting function. Further study will be required to elucidate the immunomodulatory roles and potential clinical significance of these hematologic changes in therapeutic trials of rhIL-10 in patients with chronic inflammatory and autoimmune diseases.
Huhn
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RD
Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA. richard.d.huhn@monsanto.com
Pennline
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K
Radwanski
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E
Clarke
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Sabo
R
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Cutler
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D000328:Adult; D000954:Antigens, Surface / Q000097:blood / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000097:blood; D004311:Double-Blind Method; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000097:blood; D006801:Humans; D016130:Immunophenotyping; D007275:Injections, Intravenous; D016753:Interleukin-10 / Q000493:pharmacokinetics / Q000494:pharmacology*; D007962:Leukocytes / Q000145:classification / Q000187:drug effects* / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis / Q000097:blood; D016131:Lymphocyte Subsets / Q000187:drug effects*; D010919:Placebos; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology*
D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D000949:Histocompatibility Antigens Class II; D016169:Lymphocyte Function-Associated Antigen-1; D010919:Placebos; D011994:Recombinant Proteins; D016753:Interleukin-10