The intratracheal administration of endotoxin: X. Dexamethasone downregulates neutrophil emigration and cytokine expression in vivo

Intratracheal instillation of endotoxin (LPS) causes acute pulmonary inflammation characterized by the accumulation of plasma proteins and leukocytes within the pulmonary airways. The synthetic glucocorticoid dexamethasone 1) inhibits the LPS-initiated vascular leak of plasma proteins into the airspace, 2) inhibits the LPS-initiated emigration of neutrophils and lymphocytes into the airspace in a dose-dependent fashion, and 3) inhibits LPS-initiated mRNA and/or bronchoalveolar lavage protein expression of cytokines (TNF, IL-1 and IL-6) and chemokines (MIP-l α , MIP-2 and MCP-1). In conclusion, dexamethasone inhibits both the vascular and cellular aspects of acute inflammation by downregulation of a broad spectrum of inflammatory cytokines and chemokines.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44515/1/10753_2005_Article_BF01487403.pd

Cellular and Immunologic Injury with PM-10 Inhalation

Airborne particles Jess than 10 μsm (PM-10) in mass median aerodynamic diameter (MMAD) are associated with adverse effects on human health including chronic lung diseases and mortality, but the mechanisms by which these particles might cause or aggravate diseases are not specifically known. PM-10 represents a complex mixture, both in terms of size and chemical composition, and it contains both aqueous-media soluble and insoluble particles. Furthermore, the ambient aerosol composition varies markedly in different locations and at different times in the same location. To test the effects of PM-10 on pulmonary defenses in relation to specific cell targets, barrier-reared Sprague-Dawley rats were exposed to purified air (control), to two important constituents of the fine-particle < 1 μm MMAD) fraction of PM-10-ammonium sulfate [(NH4)2SO42-] (20 or 70 μg SO42- m-3, 0.2 μm MMAD) and ammonium nitrate [NH4NO31 (90 or 350 NO3 μg m -3, 0.6 μm MMAD). Rats were also exposed to resuspended road dust (300 and 900 μg m-3, 4.0 μm MMAD), an important contributor to the coarse (> 2.5 μm MMAD) fraction of PM-10. Exposures were 4 h/day, 4 dayslwk for 8 wk. Macrophage-dependent lung defense functions (antigen binding to Fc receptors and respiratory burst activity) were significantly depressed by NOf, SO42-, and the high-concentration road dust exposures, compared to purified air controls. Lung permeability, as determined from measurements of albumin concentrations in bronchoalveolar lavage fluid, was significantly greater in rats exposed to high concentrations of road dust and NO3-, but not to SO42-, when compared to air-exposed controls. Quantitative histopathologic analyses, which included measurements of alveolar nuclear density, alveolar chord length, alveolar septal thickness, and alveolar cross sectional area, showed moderate to substantial changes. In general, the severity of the responses was in the order of SO42-NO3-road dust. The findings are consistent with those of epidemiological studies. This study also supports the hypothesis that the fine fraction of PM-10 is more toxic than the coarse fraction. © 1995 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted