Cytokines involved in the systemic inflammatory response induced by exposure to particulate Matter air pollutants (PM10)

Elevated levels of ambient particulate matter (PM10) have been associated w ith increased cardiopulmonary morbidity and mortality. We previously showed that the deposition of particles in the lung induces a systemic inflammato ry response that includes stimulation of the bone marrow. This marrow respo nse is related to mediators released by alveolar macrophages (AM) and in th is study we measured cytokines produced by human AM exposed to ambient part icles of different composition and size. Identified cytokines were also mea sured in the circulation of healthy young subjects exposed to air pollutant s during the 1997 Southeast Asian forest fires. Human AM were incubated wit h particle suspensions of residual oil fly ash (ROFA), ambient urban partic les (EHC 93), inert carbon particles, and latex particles of different size s (0.1, 1, and 10 mum) and concentrations for 24 h. Tumor necrosis factor-a lpha (TNF-alpha) increases in a dose-dependent manner when AM were exposed to EHC 93 particles (p < 0.02). The TNF response of AM exposed to different sizes of latex particles was similar. The latex (158 +/- 31%), inert carbo n (179 +/- 32%), and ROFA (216 +/- 34%) particles all show a similar maximu m TNF response (percent change from baseline) whereas EHC 93 (1,020 +/- 212 %, p < 0.05) showed a greater maximum response that was similar to lipopoly saccharicle (LPS) 1 mug/ml (812 +/- 320%). Macrophages incubated with an op timal dose of EHC 93 particles (0.1 mg/ml) also produce a broad spectrum of other proinflammatory cytokines, particularly interleukin (IL)-6 (p < 0.01 ), IL-1 beta (p < 0.05), macrophage inflammatory protein-1 alpha (MIP-1 alp ha) (p < 0.05), and granulocyte macrophage colony-stimulating factor (GM-CS F) (p < 0.01) with no difference in concentrations of the anti-inflammatory cytokine IL-10 (p = NS). Circulating levels of IL-1 beta, IL-6, and GM-CSF were elevated in subjects exposed to high levels of PM10 during an episode of acute air pollution. These results show that a range of different parti cles stimulate AM to produce proinflammatory Cytokines and these cytokines are also present in the blood of subjects during an episode of acute atmosp heric air pollution. We postulate that these cytokines induced a systemic r esponse that has an important role in the pathogenesis of the cardiopulmona ry adverse health effects associated with atmospheric pollution.