Interferon-alpha stimulates production of interleukin-10 in activated CD4(+) T cells and monocytes

被引:136
作者
Aman, MJ
Tretter, T
Eisenbeis, I
Bug, G
Decker, T
Aulitzky, WE
Tilg, H
Huber, C
Peschel, C
机构
[1] UNIV MAINZ, SCH MED, DEPT MED 3, DIV HEMATOL, D-55131 MAINZ, GERMANY
[2] UNIV INNSBRUCK, DEPT INTERNAL MED, A-6020 INNSBRUCK, AUSTRIA
关键词
D O I
10.1182/blood.V87.11.4731.bloodjournal87114731
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In the present study, we investigated the effect of interferon-alpha (IFN-alpha) on the expression of interleukin-10 (IL-10) mRNA and protein synthesis in human monocytes and CD4(+) T cells. In mononuclear cells, IFN-alpha induced expression of IL-10 mRNA and further enhanced lipopolysaccharide (LPS)-stimulated IL-10 expression. In purified monocytes, a strong expression of IL-10 mRNA induced by LPS was not further enhanced by IFN-alpha. In highly purified CD4(+) T cells, IFN-alpha upregulated IL-10 mRNA upon activation with phytohemagglutinin and phorbol myristate acetate. In purified monocytes, an effect of IFN-alpha on IL-10 protein synthesis was dependent on costimulation with LPS. Maximal stimulation of IL-10 protein by IFN-alpha was seen after prolonged incubation periods of 48 to 96 hours, whereas lFN-gamma reduced IL-10 production in the early incubation period. Similar effects of IFN-alpha were observed in CD4(+) T cells activated with CD3 and CD28 monoclonal antibodies. Addition of IFN-alpha caused an increase of IL-10 in culture supernatants of activated T-helper cells of more than 100% after 96 hours of incubation. In contrast, other cytokines, including IFN-gamma and IL-4, had no influence on IL-10 secretion stimulated by CD3 and CD28 in CD4(+) T cells. In serum samples of IFN-alpha-treated individuals, we failed to detect an influence of cytokine treatment on IL-10 serum levels, confirming the requirement of additional activating signals for IFN-alpha-mediated effects on IL-10 synthesis. In conclusion, IFN-alpha enhances the late induction of IL-10. which physiologically occurs upon stimulation of monocytes and T cells. Biologically, this effect might enhance the negative-feedback mechanism ascribed to IL-10, which limits inflammatory reactions. (C) 1996 by The American Society of Hematology.
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页码:4731 / 4736
页数:6
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