Human models of innate immunity: local and systemic inflammatory responses

We review human studies where different body sites (e.g. systemic--intravenous and local--skin or lung) are exposed to small amounts of bacterial components as a means to study innate immunity in vivo. Intravenous endotoxin administration is widely used to assess systemic inflammatory responses, and these have many similarities to those seen in early sepsis. While blood levels of cytokines, activated inflammatory cells, and stress hormones rise acutely, the alveolar space remains relatively protected from these inflammatory responses. Skin blister windows provide a means to study local neutrophil exudation without systemic inflammatory responses, and has been used to characterize defects in neutrophil transmigration. Recently, skin blister windows have been adapted to study phagocytic cell function in response to bacterial antigens in patients with cirrhosis. Inhalation of endotoxin leads to pulmonary inflammation with increases in broncho-alveolar lavage neutrophils and cytokines and mild systemic responses. Whole lung exposure to endotoxin provides a means to study the pathogenesis of occupational lung disease. These three models are important methods to study innate immune responses and their regulatory mechanisms in normal and diseased states.