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Interferon-alpha stimulates production of interleukin-10 in activated CD4+
T cells and monocytes
MJ Aman, T Tretter, I Eisenbeis, G Bug, T Decker, WE Aulitzky, H Tilg, C Huber and C Peschel
Division of Hematology, Third Department of Medicine, The Johannes
Gutenberg University School of Medicine, Mainz, Germany.
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 IFN-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.
Volume 87,
Issue 11,
pp. 4731-4736,
06/01/1996
Copyright © 1996 by The American Society of Hematology
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