AUTHOR=Stoffels Monique , Zaal Ruben , Kok Nina , van der Meer Jos W. M. , Dinarello Charles A. , Simon Anna TITLE=ATP-Induced IL-1β Specific Secretion: True Under Stringent Conditions JOURNAL=Frontiers in Immunology VOLUME=6 YEAR=2015 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2015.00054 DOI=10.3389/fimmu.2015.00054 ISSN=1664-3224 ABSTRACT=

Interleukin-1β is a potent proinflammatory cytokine, of which processing and secretion are tightly regulated. After exposure to various stimuli, mononuclear phagocytes synthesize the inactive precursor (pro-IL-1β), which is then cleaved intracellularly by caspase-1 and secreted. A widely used method for in vitro secretion of IL-1β employs LPS-primed human peripheral blood monocytes. Subsequently, adenosine triphosphate (ATP) is added to the cells in order to trigger the P2X7 receptor resulting in processing and secretion of mature IL-1β. However, it is often reported that secretion is due to cytotoxic effects of ATP with P2X7 receptor-activation-related cell death. We have challenged this concept and demonstrate IL-1β specific secretion, since there is no increase in cell death and IL-1α and IL-18 are not released in the same cultures. More importantly we show that these conclusions can only be drawn under stringent experimental conditions.