The inflammatory response in humans after inhalation of bacterial endotoxin: a review
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There is increasing evidence that diseases caused by organic dusts are mainly of an inflammatory nature. Among the many agents present in organic dusts, 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 expiratory volume in one second (FEV1), and forced vital capacity (FVC). At the alveolar level, inhalation of LPS can induce changes in the diffusion capacity. Activation and migration of neutrophils are major effects of acute LPS inhalation. Changes in mediators of inflammation, such as eosinophilic cationic protein (ECP), myeloperoxidase (MPO), interleukin-8 (IL-8), IL-1β, tumor necrosis factor α (TNFα) and C-reactive protein (CRP) in the airways and/or blood, have also been found. Inhalation of 30-40 μg LPS seems to be a threshold level for inducing clinical symptoms and lung function changes in healthy subjects. The threshold dose for inducing changes in blood neutrophils may be less than 0.5 μg LPS.¶ In conclusion, available data regarding the responses to LPS inhalation challenges demonstrate a local and a systemic inflammatory response at lower doses 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 whether the large variation between individuals in the response to organic dusts or endotoxin could be due to differences in the molecular mechanisms responsible for the toxicity of the agent.¶
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