Lipopolysaccharide challenge: immunological effects and safety in humans

Lipopolysaccharide (LPS) is a constituent of the outer membranes of Gram-negative bacteria and an important microbial trigger that stimulates innate immunity. It is ubiquitous; it can be inoculated from the environment via inhalation of dust. The resultant inflammatory responses are essential to early host defense but may also contribute to later and/or chronic organ injury. LPS challenge either intravenously or by inhalation has been widely used for the evaluation of anti-inflammatory reagents as well as to address basic scientific questions. The acute inhalation of LPS is used as a model of acute bronchitis in human volunteers. LPS inhalation is considered a well-established method that is safe and tolerable and aids in the improved characterization of anti-inflammatory drugs in proof-of-concept studies. This article reviews immunogenicity and safety data pertaining to LPS administration, with a particular focus on LPS inhalation, which may facilitate the optimization of its use in human research.