These results have led to the search for alternative enzymes that cleave pro-IL-1β, with Franchi et al identifying a synergistic interaction between inflammasome-dependent and inflammasome-independent pathways that use neutrophil elastase, proteinase-3 and matrix metalloproteinase-9.38 39 Moreover, several groups have demonstrated serine proteases to be the predominant activators of IL-1β in animal models of sterile lung injury.39 40 These inflammasome-independent pathways have not yet been investigated in humans with ARDS. The gene discussed is IL1B; the disease is acute respiratory distress syndrome.