The kinetics of grain dust-induced inflammation of the lower respiratory tract.
Deetz-DC; Jagielo-PJ; Quinn-TJ; Thorne-PS; Bleuer-SA; Schwartz-DA
Am J Respir Crit Care Med 1997 Jan; 155(1):254-259
The kinetics of grain dust induced lower respiratory tract inflammation were studied in humans and mice. Five male volunteers who never smoked, mean age 39 years, with normal baseline lung function, were exposed to an aerosolized corn dust extract (CDE) for 55 to 90 minutes at a mean target dose of 0.4 micrograms per kilogram (microg/kg) endotoxin. Exposure was by inhalation using a nebulizer or dosimeter. Spirometric evaluations and bronchoalveolar lavage were performed 1 hour preexposure and periodically from 10 minutes up to 196 hours postexposure. Male C3H/HeBFEJ-mice were exposed whole body to aerosolized CDE having a mean airborne endotoxin concentration of 8.3microg per cubic meter. The estimated endotoxin dose was 0.5microg/kg. Exposures were in a glass 75 liter exposure chamber using a nebulizer. Mice were killed at a specific time postexposure (up to 96 hours postexposure). Control mice were killed prior to exposure. Lavages (human and mice) were analyzed for changes in cellularity and tumor necrosis factor alpha (TNFa), interleukin-6 (IL6), interleukin-8 (IL8), and macrophage inflammatory protein-2 (MIP2) concentrations. In humans, CDE caused a rapid airway obstruction with decreases in 1 second forced expiratory volume and forced vital capacity persisting for up to 48 hours. CDE exposure caused similar changes in the lower respiratory tract of both humans and mice, with increases in the number of polymorphonuclear neutrophils (PMNs), peaking at 4 hours postexposure (increased for 96 hours) in humans and at 1 hour postexposure (increased for 48 hours) in mice. IL6 and TNFa concentrations increased immediately in both humans (up to 96 hours) and mice (up to 24 hours). A similar pattern of increase in IL8 concentration was seen. Maximum MIP2 concentration was seen after 24 hours persisting for 48 hours in both humans and mice. The authors conclude that single inhalation challenge with CDE induces airflow obstruction and lower respiratory tract inflammation that may persist for several days. The mouse may be a suitable model for investigating grain dust induced pulmonary inflammation.
NIOSH-Publication; NIOSH-Cooperative-Agreement; Pulmonary-system-disorders; Grain-dusts; Humans; In-vivo-studies; Laboratory-animals; Inhalation-studies; Lung-cells; Pulmonary-function-tests; Airway-obstruction; Biokinetics
American Journal of Respiratory and Critical Care Medicine
University of Iowa, Iowa City, Iowa