The inflammatory response in humans after inhalation of bacterial endotoxin: a review

There is increasing evidence that diseases caused by organic dusts are main ly of an inflammatory nature. Among the many agents present in organic dust s, bacterial endotoxin is a major candidate for the inflammatory reaction. The purpose of this paper was to review the inflammatory response in humans after inhalation of bacterial endotoxin (lipopolysaccharide, LPS) in order to improve the understanding of symptoms and reactions found among persons exposed to endotoxin-containing organic dusts. It has been reported that inhalation of LPS causes changes in forced expira tory volume in one second (FEV1), and forced vital capacity (FVC). At the a lveolar level, inhalation of LPS can induce changes in the diffusion capaci ty. Activation and migration of neutrophils are major effects of acute LPS inhalation. Changes in mediators of inflammation, such as eosinophilic cati onic protein (ECP), myeloperoxidase (MPO), interleukin-8 (IL-8), IL-1 beta, tumor necrosis factor alpha (TNF alpha) and C-reactive protein (CRP) in th e airways and/or blood, have also been found. Inhalation of 30-40 mug LPS s eems to be a threshold level for inducing clinical symptoms and lung functi on changes in healthy subjects. The threshold dose for inducing changes in blood neutrophils may be less than 0.5 mug LPS. In conclusion, available data regarding the responses to LPS inhalation cha llenges demonstrate a local and a systemic inflammatory response at lower d oses of LPS, while higher inhaled doses are required to elicit significant clinical and lung function responses. Future inhalation studies on LPS need to focus on relevant diagnostic tools for the inflammatory reaction among persons exposed to endotoxin-containing organic dusts and to evaluate wheth er the large variation between individuals in the response to organic dusts or endotoxin could be due to differences in the molecular mechanisms respo nsible for the toxicity of the agent.