Endotoxin responsiveness and grain dust-induced inflammation in the lower respiratory tract.
Schwartz-DA; Thorne-PS; Jagielo-PJ; White-GE; Bleuer-SA; Frees-KL
Am J Physiol, Lung Cell Mol Physiol 1994 Nov; 267(5):L609-L617
Two models of endotoxin hyporesponsiveness were used to identify the role of endotoxin in grain dust induced airway disease in mice. In the first model, the inflammatory response in the lower airways of endotoxin sensitive (C3H/HeBFEJ) and endotoxin resistant (C3H/HeJ) male mice was compared after inhalation of sterile saline, lipopolysaccharide (LPS), corn dust extract (CDE), and sterile corn dust extract (SCDE). The second model investigated whether acquired endotoxin hyporesponsiveness altered the inflammatory response to sterile corn dust extract. Statistically significant differences in the concentration of total cells, neutrophils and tumor necrosis factor alpha (TNF-alpha) in bronchial lavage fluid occurred in endotoxin sensitive mice when endotoxin, SCDE and CDE solutions exceeded 0.30 micrograms/meter squared. When the mice were challenged with Escherichia-coli LPS, similar results occurred. The absolute differences in measures of inflammation in the lower airways between the endotoxin sensitive and resistant mice reached at least two orders of magnitude at higher concentrations. A dose response relationship existed in the endotoxin sensitive mice exposed to LPS, SCDE, and CDE. The endotoxin resistant mice only showed a significant increase in TNF-alpha after high concentrations of SCDE or CDE. Acquired tolerance to endotoxin significantly reduced the inflammatory response to inhaled corn dust. Endotoxin sensitive mice pretreated with intraperitoneal LPS demonstrated a 60 fold decrease in TNF-alpha when parenterally administered endotoxin compared to control endotoxin sensitive mice pretreated with saline. The mice made tolerant also showed reduced concentrations of lavage cells when exposed to inhaled LPS or SCDE, and each measure of inflammation was reduced by 50% or more, compared to control mice. The authors conclude that endotoxin appears to be the principal component of grain dust that causes inflammatory responses in the lower respiratory tract.
NIOSH-Publication; NIOSH-Cooperative-Agreement; Laboratory-animals; Endotoxins; Dust-inhalation; Respirable-dust; Grain-dusts; Respiratory-hypersensitivity; Lung-disorders; Lung-cells; Immunotoxins; Inhalation-studies;
Author Keywords: airflow obstruction; lipopolysaccharide; airway inflammation organic dust
David A. Schwartz, Departments of Internal Medicine and Preventive Medicine and Environmental Health, The University of Iowa College of Medicine, Iowa City, Iowa 52242
American Journal of Physiology: Lung Cellular and Molecular Physiology
University of Iowa, Iowa City, Iowa