Increased Susceptibility and Severity of Influenza in Mice Exposed to Diesel Exhaust.
Epidemiological studies have noted an increase in adverse health effects with increasing levels of air pollution. One major area of concern is the incidence of respiratory infections, specifically influenza. An air pollutant that has raised concern in recent years is diesel exhaust (DE) due to an increase the amount of diesel engines in use. Previous laboratory studies have reported that DE exposure prior to an influenza infection increases viral titers but the mechanism of how this occurs is still unknown. Herein, studies were designed to investigate three main areas associated with DE enhanced influenza infection. 1) Assess whether DE affects host defense responses against pathogens, 2) Determine if pre-exposure to DE increases susceptibility to influenza in vivo, 3) Investigate whether exposure to DE increases the severity of an ongoing established influenza infection. DE exposure alone increased proinflammatory cytokines, adhesion molecules, decreased expression and production of surfactant proteins (SP)-A and D as well as clara cell secretory protein (CCSP). The molecules downregulated by DE are important for binding viral and bacterial pathogens therefore making the lung more susceptible to infection. This was confirmed when mice were exposed to DE and then subsequently infected with influenza A. One day post infection mice pre-exposed to DE had a significant increases in influenza induced inflammation and viral titers that were associated with a decrease in SP-A and SP-D. Mice exposed to DE during an established influenza infection also had a significant increase in viral titers and pulmonary inflammation throughout the course of infection. This DE-enhanced influenza infection was associated with an upregulation of the Th2 cytokine IL-4 which has previously been shown to delay clearance. However with antioxidant treatment to combat the oxidative stress induced by DE, pulmonary inflammation and IL-4 expression returned to baseline levels. Taken together these data indicate that exposure to DE either before or during influenza infection has immunomodulatory effects that can be detrimental to the host with increased viral proliferation and morbidity associated with the disease.
Advisor:Dr. Susan Tonkonogy; Dr. Matt Koci; Dr. Ilona Jaspers; Dr. Mac Law; Dr. Ian Gilmour
School:North Carolina State University
School Location:USA - North Carolina
Source Type:Master's Thesis
Date of Publication:12/02/2008