In utero exposure to diesel exhaust particles, but not silica, alters post-natal immune development and function.

Our understanding of the impact of in utero exposure to PM on post-natal immune function and the subsequent response to PM exposure is limited. Similarly, very few studies have considered the effect of exposure to PM from different sources. Thus, the aim of this study was to examine how in utero exposure to PM from different sources effects the post-natal response to pro-inflammatory and immune stimuli. C56BL/6J pregnant mice were exposed intranasally on gestational day (E)7.5, E12.5 and E17.5-50 µg of diesel exhaust particles (DEP), silica or saline. At 4-weeks post-natal age, sub-groups of male and female mice were exposed intranasally to 50 µg of DEP or saline. Lung inflammatory responses were assessed 6 h later by quantifying inflammatory cells and cytokine production (MCP-1, MIP-2, IL-6). In separate groups of mice, the spleen was harvested to quantify B and T cell populations. Splenocytes were isolated and exposed to lipopolysaccharide or poly I:C for assessment of cytokine production. Exposure to DEP in utero decreased %CD1dhighCD5+ B cells in female mice and IFN-γ production by splenocytes in both sexes. Male mice had elevations in macrophage and lymphocyte numbers in response to DEP whereas female mice only had elevated IL-6, MCP-1 and MIP-2 levels. In utero exposure to silica had no effect on these measures. These data suggest that in utero exposure to PM alters immune development and post-natal immune function. This response is dependent on the source of PM, which has implications for understanding the community health effects of exposure to air pollution.

Pregnancy protects against the pro-inflammatory respiratory responses induced by particulate matter exposure.

BACKGROUND: Little is known about the effect of pregnancy on the response to particulate matter. The aim of this study was to determine if pregnancy increases the susceptibility to PM from different sources using a mouse model. METHODS: Pregnant, eight-week-old C57BL/6J mice were exposed intranasally to 50 µg of diesel exhaust particles (DEP), iron oxide (Fe2O3) or silica (SiO2) in 50 µL of saline, or saline alone, on gestational day (E)7.5, E12.5 and E17.5. Groups of non-pregnant mice were exposed on day (D)0, D5 and D10. Biological samples were collected 24 h after the last exposure. Serum IL-4 and IL-6 levels were quantified by ELISA. Bronchoalveolar lavage (BAL) fluid was collected for inflammatory cells counts and assessment of IFN-É£, IL-4, IL-5, IL-6, IL-8 and IL-10 levels by ELISA. The spleen and thymus were also collected and the percentage of B cells and CD4+, CD8+ and CD4+CD25 + T cells were determined by flow cytometry. RESULTS: Exposure to silica caused an influx of lymphocytes, eosinophils and neutrophils into the lung. The magnitude of this response was suppressed by pregnancy. Pregnancy also enhanced the production of CD4+CD25 + T cells in response to DEP and silica exposure. CONCLUSIONS: Collectively, our data suggest that pregnancy reduces the inflammatory response to silica and alters the immune response to DEP. These responses were accompanied by pregnancy related changes including increased IL-4 production, reduced IL-8 production and an increase in the proportion of CD4+CD25 + T cells in response to PM exposure.