IFN-alpha 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.
Administration of IFN-gamma and IFN-alpha may protect or induce autoimmune diseases. Although the in vitro regulation of monokine secretion by IFN-gamma have been extensively studied, the regulatory function of IFN-alpha has not yet been elucidated. We compared IFN-alpha and IFN-gamma, 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-alpha 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-alpha priming for TNF-alpha secretion; 2) pretreatment of monocytes with IFN-alpha 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-alpha and IFN-gamma 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-alpha, IFN-gamma primes monocytes to enhance LPS- or SAC-induced TNF-alpha and IL-12 production, but surprisingly, it increases IL-10 production by monocytes following LPS but not SAC stimulation; and finally, 5) IFN-alpha 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-alpha therapy.
University of Montreal, Louis-Charles Simard Research Center, Notre-Dame Hospital, Montreal, Canada.
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P
Hermann
M
M
Rubio
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T
Nakajima
G
G
Delespesse
M
M
Sarfati
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D017951:Antigen Presentation / Q000187:drug effects; D018122:B7-1 Antigen / Q000096:biosynthesis*; D004926:Escherichia coli / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000187:drug effects; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism* / Q000502:physiology; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects
D000276:Adjuvants, Immunologic; D018122:B7-1 Antigen; D015395:Histocompatibility Antigens Class I; D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma