The Response to Acute and Chronic Exposure to Inhaled Endotoxin in Humans

The first controlled exposure to purified endotoxin by inhalation, in human, was reported by Cavagna et al. He has shown that 80 µg inhaled LPS was associated with a bronchoconstriction. The reaction was more pronounced in chronic bronchitis compared to healthy subjects. In 1982, van der Zwan et al demonstrated, in humans, that inhaled endotoxin induced a blood leucocytosis while a bronchoconstriction was limited to the subjects characterized by a significant non specific airways’ responsiveness. Since then, many papers have been published that characterize the clinical, physiological and inflammatory response to inhaled endotoxin in healthy subjects.
Inhalation of pure endotoxin may elicit, in some individuals, dyspnea, chest tightness, myalgia, shivers, fatigue and malaise with fever. In human subjects, inhalation of pure endotoxin was associated with bronchoconstriction, a change in non-specific airway responsiveness and reduction in alveolar-capillary diffusion.
Local and systemic inflammatory responses have been measured after endotoxin inhalation in normal and asthmatic subjects. At the blood level, a significant neutrophilia with an expression of the acute phase proteins CRP and LBP, were observed 4 to 8 hours after inhalation of endotoxin both in normal and asthmatic subjects. The increase of the plasma 16kDa Clara cell protein suggests significant change in the permeability of the alveolocapillary barrier. At the airways level, an increase in cytokines, chemokines, neutrophils and monocytes in the induced sputum was observed 6 and 24 hours after inhaled endotoxin. […]