Schematic representative of the in vivo data. Our data suggests that in the mouse inhaled LPS activates TLR4 in the airway to trigger MyD88 dependent increase mRNA production of pro-IL-1α, pro-IL-1β, pro-Caspase 1, pro-caspase 11, ASC and NALP3, but not pro-IL-18 or IPAF. These increases in mRNA levels are likely to be associated with an increase in the corresponding protein levels. The pro-Caspase 1, pro-caspase 11, ASC and NALP3 are then primed ready for a second stimulus (i.e. via ATP-P2X7) and subsequent processing of pro-IL-1β and pro-IL-18. The LPS stimulus causes caspase 1/caspase 11 independent release of IL-1α, IL-1β and IL-18 into the airway lumen (either in the pro or mature form), of which the latter two appear to require IPAF. Pro-forms of the cytokines could be cleaved to the mature forms outside the cell.