Cytokine gene expression after inhalation of corn dust.

Abstract

To characterize the time course and localize the production of proinflammatory cytokines after inhalation of corn dust, we exposed mice (C3H/HeBFeJ) by inhalation challenge to sterile corn dust extract (CDE) and contrasted this response to inhalation of Escherichia coli 0111:B4 lipopolysaccharide (LPS) or pyrogen-free saline. After both CDE and LPS exposure, an increase in the concentration of bronchoalveolar lavage neutrophils was detected 1 h postinhalation and persisted for 48 h. Significant increases in the bronchoalveolar lavage concentration of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, and macrophage inflammatory protein (MIP)-2 resulted after inhalation of either CDE or LPS. Although the time courses of these cytokines were distinct, a similar pattern of release was observed after both CDE and LPS exposure. A single inhalation exposure of either CDE or LPS resulted in enhanced expression of mRNA for TNF-alpha, IL-1alpha, and MIP-2 that was evident and most pronounced within 1 h of the inhalation challenge. Although enhanced expression of mRNA for TNF-alpha was detectable 12 h after completion of the inhalation challenge, IL-1alpha and MIP-2 mRNA expression remained elevated through the 24-h time point. TNF-alpha, IL-1alpha, and MIP-2 expression was localized by in situ hybridization to inflammatory cells in the airways and alveoli from 1 to 24 h in both CDE- and LPS-exposed lungs. Interestingly, there was no convincing evidence that MIP-2 was substantially produced by airway epithelial cells. The pattern, timing, and location of expression of TNF-alpha, IL-1alpha, and MIP-2 mRNA after a single inhalation exposure of CDE in comparison with LPS is similar, supporting a common etiology and mechanism of inflammation in the lower respiratory tract. Moreover, our findings indicate that inhalation of corn dust or LPS results in an acute inflammatory process that is primarily mediated by inflammatory cells and appears to be self-limited.