Differential requirement for the activation of the inflammasome for processing and release of IL-1β in monocytes and macrophages

The processing of pro-interleukin-1 beta depends on activation of caspase-1. Controversy has arisen whether Toll-like receptor (TLR) ligands alone can activate caspase-1 for release of interleukin-1 beta (IL-1 beta). Here we demonstrate that human blood monocytes release processed IL-1 beta after a one-time stimulation with either TLR2 or TLR4 ligands, resulting from constitutively activated caspase-1 and release of endogenous adenosine triphosphate. The constitutive activation of caspase-1 depends on the inflammasome components, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and NALP3, but in monocytes caspase-1 activation is uncoupled from pathogen-associated molecular pattern recognition. In contrast, macrophages are unable to process and release IL-1 beta solely by TLR ligands and require a second adenosine triphosphate stimulation. We conclude that IL-1 beta production is differentially regulated in monocytes and macrophages, and this reflects their separate functions in host defense and inflammation. (Blood. 2009; 113: 2324-2335)