Interferon-α stimulates production of interleukin-10 in activated CD4⁺ T cells and monocytes

In the present study, we investigated the effect of interferonα (IFN-α) on the expression of interleukin-10 (IL-10) mRNA and protein synthesis in human monocytes and CD4⁺ T cells. In mononuclear cells, IFN-α 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-α. In highly purified CD4⁺ T cells, IFN-α upregulated IL-10 mRNA upon activation with phytohemagglutinin and phorbol myristate acetate. In purified monocytes, an effect of IFN-α on IL-10 protein synthesis was dependent on costimulation with LPS. Maximal stimulation of IL-10 protein by IFN-α was seen after prolonged incubation periods of 48 to 96 hours, whereas IFN-γ reduced IL-10 production in the early incubation period. Similar effects of IFN-α were observed in CD4⁺ T cells activated with CD3 and CD28 monoclonal antibodies. Addition of IFN-α 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-γ and IL-4, had no influence on IL- 10 secretion stimulated by CD3 and CD28 in CD4⁺ T cells. In serum samples of IFN-α-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-α-mediated effects on IL-10 synthesis. In conclusion, IFN-α 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.