The study that L.C. Loh describes in his letter above adds another interesting aspect that is critical for the response to inhaled endotoxin.
Lipopolysaccharide tolerance is a well-known feature of several host defence cells, although the mechanisms involved are not entirely clear 1. Tolerance has also been shown to be associated with various cellular processes, such as decreased activity of Gi proteins, protein kinase C, mitogen-activated protein kinase, activator protein-1 and nuclear factor-κB (NF-κB). Inhibitory molecules such as IRAK-M, suppressor of cytokine-signaling-1 and inhibitor-κB are found activated. At the nuclear level, the NF-κB subunit p50 homodimer expression and peroxisome-proliferator-activated receptors-γ are increased. There is evidence from rodent studies that this phenomenon is also relevant for pulmonary innate immunity 2.
The preliminary results described in this letter support this view and it is likely that this mechanism is of biological relevance, because the lung is constantly exposed to small amounts of lipopolysaccharide. The pulmonary exposure with endotoxin probably has many consequences. At this time it is uncertain where lipopolysaccharide tolerance is functionally located in this scenario.
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