Lipopolysaccharide challenge of humans as a model for chronic obstructive lung disease exacerbations.

Endotoxin, or lipopolysaccharide (LPS), is a constituent of the outer cell membrane of Gram-negative bacteria. LPS is a highly potent proinflammatory substance, that, when inhaled, dose-dependently causes fever, chills, and bronchoconstriction. These symptoms are accompanied by a proinflammatory response in sputum and bronchoalveolar lavage fluid with elevation of neutrophils, macrophages and certain cytokines/chemokines. This response can be partially modified with certain drugs. Similar inflammatory changes are observed both in the stable state of chronic obstructive lung disease (COPD) and during exacerbations of this disease. Cigarette smoke, which contains bioactive LPS, is the most common cause of COPD and may also precipitate exacerbations. In addition, the presence of Gram-negative bacteria in the lower airways is a distinguishing feature both of stable COPD and of exacerbations. Based on this knowledge we argue here that inhaled LPS provocation of healthy volunteers can be used as a model or COPD as well as for exacerbations of this disease.