The kinetics of grain dust-induced inflammation of the lower respiratory tract

To characterize the kinetics of grain dust-induced airflow obstruction and inflammation in the lower respiratory tract, we performed serial spirometry and bronchoalveolar lavage (BAL) in human subjects and whole-lung lavage in mice following a single inhalation exposure to comparable dosages of corn dust extract (CDE). Following inhalation of CDE, our human study subjects developed significant airflow obstruction 10 min postexposure which persisted for 48 h. Human subjects and mice had similar acute and persistent changes in lavage cellularity after exposure to CDE. A profound increase in the concentration of lavage neutrophils was present in the initial postexposure lavage in both human subjects and mice. This increase persisted for 96 h in human subjects and 48 h in mice. Small but significant increases in lavage macrophage concentration were present 48 h postexposure in human subjects and at 96 h postexposure in mice. Inhalation of CDE resulted in a significant increase in the concentration of proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in the lavage fluid of both human subjects and mice. Similarly, significant increases in lavage concentrations of IL-8 in humans and macrophage inflammatory protein-2 (MIP-2) in mice occurred after inhalation of CDE. The lavage concentration of all measured proinflammatory cytokines returned to baseline levels by 168 h in humans and 96 h in mice. These findings suggest that a single inhalation challenge of CDE results in airflow obstruction and lower respiratory tract inflammation that may last for several days. These physiologic and inflammatory responses appear to be self-limited with no evidence of persistent injury 1 wk after the inhalation challenge. Moreover, the inflammatory response in the lower respiratory tract after inhalation of grain dust is similar in human subjects and mice, suggesting that the mouse may be an appropriate model for further investigation of grain dust-induced inflammation.