Summary Recent studies on endotoxin/lipopolysaccharide (LPS)‐induced acute inflammatory response in the lung are reviewed. The acute airway inflammatory response to inhaled endotoxin is mediated through Toll‐like receptor 4 (TLR4) and CD14 signalling as mice deficient for TLR4 or CD14 are unresponsive to endotoxin. Acute bronchoconstriction, tumour necrosis factor (TNF), interleukin (IL)‐12 and keratinocyte‐derived chemokine (KC) production, protein leak and neutrophil recruitment in the lung are abrogated in mice deficient for the adaptor molecules myeloid differentiation factor 88 (MyD88) and Toll/Interleukin‐1 receptor (TIR)‐domain‐containing adaptor protein (TIRAP), but independent of TIR‐domain‐containing adaptor‐inducing interferon‐beta (TRIF). In particular, LPS‐induced TNF is required for bronchoconstriction, but dispensable for inflammatory cell recruitment. Lipopolysaccharide induces activation of the p38 mitogen‐activated protein kinase (MAPK). Inhibition of pulmonary MAPK activity abrogates LPS‐induced TNF production, bronchoconstriction, neutrophil recruitment into the lungs and broncho‐alveolar space. In conclusion, TLR4‐mediated, bronchoconstriction and acute inflammatory lung pathology to inhaled endotoxin are dependent on TLR4/CD14/MD2 expression using the adapter proteins TIRAP and MyD88, while TRIF, IL‐1R1 or IL‐18R signalling pathways are dispensable. Further downstream in this axis of signalling, TNF blockade reduces only acute bronchoconstriction, while MAPK inhibition abrogates completely endotoxin‐induced inflammation.

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These results indicate that ASC has a profound inhibitory effect on lung inflammation and hyper-responsiveness and that suppression of IL-5 or IL-4 and of eotaxin contributes to this effect.

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