TLR4 and acute respiratory distress syndrome: Caspase-1 and IL-18 promote ARDS development, and circulating IL-18 levels have been associated with disease severity and mortality.260 The recognition of LPS by TLR4 activates the NLRP3 inflammasome, as well as IL-1R1 expression on alveolar macrophage surfaces via the MyD88/NF-κB dependent pathway.261 LPS-TLR4 signals alveolar macrophages that increase ARDS by upregulating IL-1β-IL-1RI signaling.