Instillation of Coarse Ash Particulate Matter and Lipopolysaccharide Produces a Systemic Inflammatory Response in Mice

Abstract

Coronary ischemic events increase significantly following a “bad air” day. Ambient particulate matter (PM₁₀) is the pollutant most strongly associated with these events. PM₁₀ produces inflammatory injury to the lower airways. It is not clear, however, whether pulmonary inflammation translates to a systemic response. Lipopolysaccharide (LPS) is a proinflammatory molecule often associated with the coarse fraction of PM. It was hypothesized that PM>2.5 from coal plus LPS induce pulmonary inflammation leading to a systemic inflammatory response. Mice were intratracheally instilled with saline, PM (200 μg), PM + LPS10 (PM + 10 μg LPS), or PM + LPS100 (PM + 100 μg LPS). Eighteen hours later, histologic analysis was performed on lungs from each group. Pulmonary and systemic inflammation were assessed by measuring the proinflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the pulmonary supernatant and plasma. In a follow-up study, the effects of LPS alone were assessed. Histologic analysis revealed a dose-dependent elevation in pulmonary inflammation with all treatments. Pulmonary TNF-α and IL-6 both increased significantly with PM + LPS100 treatment. Regarding plasma, TNF-α significantly increased in both PM + LPS10 and PM + LPS100 treatments. For plasma IL-6, all groups tended to rise with a significant increase in the PM + LPS100 group. The results of the follow-up study indicate that the responses to PM + LPS were not due to LPS alone. These results suggest that coarse coal fly ash PM>2.5 combined with LPS produced pulmonary and systemic inflammatory responses. The resulting low-level systemic inflammation may contribute to the increased severity of ischemic heart disease observed immediately following a bad air day.

The authors thank Doug Cromey, MS, for performing the pulmonary histology. This work was supported by a grant from the Arizona Biomedical Research Commission, the Allan C. Hudson and Helen Lovaas Endowment, and the Southwest Environmental Health Sciences Center, grant NIH ES 06694.