Finnerty K, Choi JE, Lau A, Davis-Gorman G, Diven C, Seaver N, Linak WP, Witten M, McDonagh PF. 2007. Instillation of coarse ash particulate matter and lipopolysaccharide produces a systemic inflammatory response in mice. J Toxicol Environ Health Part A 70:1957–1966, doi: 10.1080/15287390701549229.
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.