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IFN-gamma enhances production of IFN-alpha in human macrophages but not in monocytes
1National Public Health Institute, Helsinki, Finland.
Abstract:
Monocytes/macrophages are efficient producers of alpha interferons (IFN), and IFN-gamma is a potent activator of these cells. The present study sought to investigate whether IFN-alpha affects the capacity of human monocytes/macrophages to produce IFN-alpha on induction with Sendai virus. Plastic-adherent human peripheral blood monocytes were grown in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) for 3 weeks during which they were transformed into macrophages. At various times, the cultures were pretreated for 24 h with IFN-gamma and induced with Sendai virus for IFN-alpha production. Pretreatment with IFN-gamma had no effect on the production of IFN-alpha during the first days in culture. The production of IFN-alpha was thereafter significantly enhanced by the IFN-gamma pretreatment. Minute amounts of IFN-gamma, < or = 0.1 IU/ml, increased the production of IFN-alpha in macrophages cultured for more than 7 days. The cooperation between IFN-gamma and IFN-alpha in macrophages may play a role in the antiviral defense of the body.
Insights
Interferon-gamma (IFN-gamma) enhances the ability of human macrophages to produce interferon-alpha (IFN-alpha) when stimulated with Sendai virus, particularly in longer-term cultures.
Area of Science:
- Immunology
- Cell Biology
- Virology
Background:
- Monocytes and macrophages are key producers of alpha interferons (IFN-alpha).
- Interferon-gamma (IFN-gamma) is known to activate monocytes/macrophages.
Purpose of the Study:
- To determine if IFN-alpha production by human monocytes/macrophages is affected by IFN-gamma pretreatment.
- To investigate the role of Sendai virus induction in this interaction.
Main Methods:
- Human peripheral blood monocytes were cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) for 3 weeks to differentiate into macrophages.
- Macrophages were pretreated with IFN-gamma for 24 hours.
- IFN-alpha production was induced using Sendai virus.
Main Results:
- IFN-gamma pretreatment did not affect early IFN-alpha production.
- IFN-alpha production was significantly enhanced by IFN-gamma in macrophages cultured for over 7 days.
- Low concentrations of IFN-gamma (< or = 0.1 IU/ml) were sufficient to enhance production in mature macrophages.
Conclusions:
- IFN-gamma enhances the capacity of human macrophages to produce IFN-alpha upon viral induction.
- This synergistic interaction between IFN-gamma and IFN-alpha may be crucial for effective antiviral defense.
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