IFN-α Priming of Human Monocytes Differentially Regulates Gram-Positive and Gram-Negative Bacteria-Induced IL-10 Release and Selectively Enhances IL-12p70, CD80, and MHC Class I Expression

Abstract

Administration of IFN-γ and IFN-α may protect or induce autoimmune diseases. Although the in vitro regulation of monokine secretion by IFN-γ have been extensively studied, the regulatory function of IFN-α has not yet been elucidated. We compared IFN-α and IFN-γ, added alone or simultaneously before bacterial stimulation, for the control of monokine release and the expression of costimulatory molecules by human monocytes. Our data show that: 1) IFN-α primes monocytes for increased production of IL-10 in response to Staphylococcus aureus Cowan I strain (SAC) but not to LPS, leading to a lack of IFN-α priming for TNF-α secretion; 2) pretreatment of monocytes with IFN-α inhibits LPS- or SAC-induced IL-12p40 production but unexpectedly enhances the release of the biologically active form of IL-12 (IL-12p70); 3) IFN-α and IFN-γ exert an antagonistic effect on LPS- and SAC-induced IL-10 as well as IL-12p40 release, whereas they further enhance IL-12p70 production when added simultaneously; 4) in contrast to IFN-α, IFN-γ primes monocytes to enhance LPS- or SAC-induced TNF-α and IL-12 production, but surprisingly, it increases IL-10 production by monocytes following LPS but not SAC stimulation; and finally, 5) IFN-α pretreatment selectively up-regulates CD80 and MHC class I expression on monocytes. It is proposed that the outcome of the immune response at the site of inflammation may depend on both the type of bacterial injury (Gram-positive or -negative) and of locally produced IFNs, and that the differential and opposite effects of type I and type II IFNs on monocytes may account for the beneficial or detrimental effects of IFN-α therapy.