Modulation of pulmonary inflammatory responses and antimicrobial defenses in mice exposed to diesel exhaust

Toxicol Appl Pharmacol. 2008 Jun 15;229(3):310-9. doi: 10.1016/j.taap.2008.01.040. Epub 2008 Feb 15.


Diesel exhaust (DE) is a major component of urban air pollution and has been shown to increase the severity of infectious and allergic lung disease. The purpose of this study was to evaluate the effects of DE exposure on pulmonary inflammation, mediator production and antimicrobial defenses in an exposure model that had previously been shown to increase susceptibility to influenza. BALB/c mice were exposed to filtered air, or to DE diluted to yield 0.5 or 2 mg/m(3) of diesel exhaust particles (DEP) for 4 h per day for 1 or 5 days. Immediately and 18 h after one or five diesel exposures mice were euthanized to assess both immediate and delayed effects. DE exposure for 5 days at either concentration caused higher neutrophil numbers and lesion scoring compared to air controls. Intracellular adhesion molecule-1 (ICAM-1), which recruits inflammatory cells and is an entry site for rhinoviruses was increased immediately after 1 or 5 days of DE exposure. Several inflammatory and immune cytokines (TNF-alpha, MIP-2, IL-6, IFN-gamma, and IL-13) were also upregulated at various time points and concentrations. In contrast, clara cell secretory protein (CCSP), surfactant protein A (SP-A), and surfactant protein D (SP-D) which are important host defense molecules, were significantly decreased at both the message and protein level with DE exposure. We conclude that exposure to moderate and high occupational levels of DE caused an increase in lung injury and inflammation, and a decrease in host defense molecules, which could result in increased susceptibility to respiratory pathogens.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Air Pollutants / toxicity*
  • Animals
  • Cytokines / drug effects
  • Cytokines / metabolism
  • Female
  • Intercellular Adhesion Molecule-1 / drug effects
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lung / drug effects*
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Occupational Exposure / adverse effects
  • Pneumonia / chemically induced*
  • Pulmonary Surfactant-Associated Protein A / drug effects
  • Pulmonary Surfactant-Associated Protein A / metabolism
  • Pulmonary Surfactant-Associated Protein D / drug effects
  • Pulmonary Surfactant-Associated Protein D / metabolism
  • Respiratory Tract Infections / etiology
  • Time Factors
  • Up-Regulation / drug effects
  • Uteroglobin / drug effects
  • Uteroglobin / metabolism
  • Vehicle Emissions / toxicity*


  • Air Pollutants
  • Cytokines
  • Pulmonary Surfactant-Associated Protein A
  • Pulmonary Surfactant-Associated Protein D
  • Scgb1a1 protein, mouse
  • Vehicle Emissions
  • Intercellular Adhesion Molecule-1
  • Uteroglobin