In conclusion, By revisiting (25) a two hit model (Poly(I:C)-MTV) of acute lung injury noted to be TLR4 independent, we have detected an additional stimulus, e.g. systemic endotoxemia; as a result of gut-lung axis, both non-canonical caspase-11 [via presumptive cytosolic endotoxemia (28)] and canonical [via NLRP3 inflammasome (38, 39)] and their interactions led to pyroptosis in alveolar macrophages, disruption of alveolar capillary barrier and proinflammatory state within lung. The gene discussed is TLR4; the disease is serum lipopolysaccharide activity.