Peripheral blood markers of central nervous system effects following controlled human exposure to diesel exhaust

Epidemiological and animal studies suggest that exposure to airborne pollutants may negatively impact the central nervous system (CNS). It is thought that traffic related air pollution (TRAP), and other forms of combustion-derived pollutants, may induce a maladaptive activation of the CNS immune system, however, the exact pathway is not understood. Animal models and epidemiological studies have inherent limitations including potential interspecies differences and residual confounding. Given this, the aim of this research is to examine effects of TRAP on the CNS using a controlled human exposure. 27 healthy adults were exposed to two conditions: filtered air (FA) and diesel exhaust (DE) (300µg PM₂.₅/m³) for 120 minutes, in a double-blinded crossover study with exposures separated by four-weeks. Prior to and at 0, 3, and 24 hours following exposure, serum and plasma were collected and analyzed for inflammatory cytokines IL-6 and TNF-α, the astrocytic protein S100b, the neuronal cytoplasmic enzyme neuron specific enolase (NSE), and brain derived neurotrophic factor (BDNF). The hypothesis was that IL-6, TNF-α, S100b and NSE would increase and BDNF would decrease following DE exposure. Changes in levels of biomarkers were assessed using a paired t-test to compare the change from baseline at each post-exposure timepoint following DE or FA exposure. A linear mixed effects model was build including exposure and timepoint as covariates, and subject ID as a random effect. Age and gender were examined as potential effect-modifying variables. At no time-point following exposure to DE was a significant increase from baseline seen for IL-6, TNF-α, S100b or NSE, or decrease for BDNF, relative to FA exposure. The linear mixed effects model revealed indication of diurnal behavior for S100B, NSE and BDNF; however, no significant exposure-time-point interaction, suggesting the biomarkers were not affected by DE exposure. These results indicate that short-term exposure to DE amongst young, healthy adults does not acutely affect levels of the measured biomarkers. This study does not disprove a relationship between air pollution and adverse CNS effects and suggests a need to examine the effects of TRAP on the brain using in chronic exposure models or more sensitive CNS endpoints.Medicine, Faculty ofPopulation and Public Health (SPPH), School ofGraduat