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

The processing of pro-interleukin-1βp depends on activation of caspase-1. Controversy has arisen whether Toll-like receptor (TLR) ligands alone can activate caspase-1 for release of interleukin-1βp(IL-1β). Here we demonstrate that human blood monocytes release processed IL-1β after a one-time stimulation with either TLR2 or TLR4 ligands, resulting from constitutively activated caspase-1 and release of endogenous adenosine tri-phosphate. The constitutive activation of caspase-1 depends on the inflamma-some 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 β solely by TLR ligands and require a second adenosine triphosphate stimulation. We conclude that IL-1 β production is differentially regulated in monocytes and macrophages, and this reflects their separate functions in host defense cand inflammation. (Blood. 2009;113:2324-2335)