In vivo effects of recombinant human interleukin-10 on lymphocyte phenotypes and leukocyte activation markers in inflammatory bowel disease.
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BACKGROUND: Interleukin-10 (IL-10) exhibits potent anti-inflammatory and immunosuppressive activities in vitro. Recent data indicate that treatment with recombinant human IL-10 (rHuIL-10) Crohn's disease is safe and may induce clinical and endoscopic remission. The present study investigates the in vivo immunomodulatory properties of rHuIL-10 in inflammatory bowel disease (IBD). METHODS: As part of two randomized, double-blinded, placebo-controlled trials, repeated flow cytometric analyses of lymphocyte phenotypes (CD3, CD4, CD8, CD16 + 56, CD19) and activity markers (human leukocyte antigen [HLA]-DR; intercellular adhesion molecule-1 [ICAM-1]; IL-2-receptor alpha [IL-2R alpha]; high affinity receptor for immunoglobulin G [IgG; Fc gamma RI]) on T cells, monocytes, and neutrophils were performed in 17 patients with IBD who received rHuIL-10 (5, 10, or 20 micrograms/kg) or placebo, administered subcutaneously, once daily for 28 days. RESULTS: Minor changes were noted in CD3+, CD8+, and CD3+/CD16 + 56+ lymphocyte phenotypes, whereas absolute numbers of CD4+ lymphocytes and CD19+ cells increased. T-cell activation markers HLA-DR and IL-2R alpha were downregulated. rHuIL-10 did not influence HLA-DR expression on monocytes. ICAM-1 modulation on monocytes and neutrophils was mild and inconsistent. Fc gamma RI expression was upregulated on both neutrophils and monocytes. CONCLUSIONS: These data indicate that the immunosuppressive effects of rHuIL-10 treatment are partly different from its in vitro observed actions. The increase of the cytotoxicity-mediating Fc gamma RI points to potential immunostimulating properties of this cytokine.
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