Ozone augments interleukin-8 production induced by ambient particulate matter

Experimental and controlled human exposure studies have demonstrated additive effects of ambient particulate matter and ozone on health. A few epidemiological studies have suggested that ambient particulate matter components are important for the combined effects of ambient particulate matter and ozone on health. However, few studies have examined whether ozone changes the effects of ambient particulate matter on pro-inflammatory cytokine production. In this study, the influence of ozone on pro-inflammatory cytokine production in response to ambient particulate matter was evaluated. Ambient particulate matter smaller than 1 μm was collected and the suspension of this particulate matter was bubbled through 0.12 ppm and 0.24 ppm ozone. THP1 cells were stimulated by the solution containing the particulate matter with and without bubbling through ozone at 1 μg/mL. The interleukin-8 concentrations in the supernatants of THP1 cells stimulated by collected particulate matter dissolved in solution were 108.3 ± 24.7 pg/mL without ozone exposure, 165.0 ± 26.1 pg/mL for 0.12 ppm ozone bubbling for 1 min, 175.1 ± 33.1 pg/mL for 0.12 ppm for 5 min, 183.3 ± 17.8 pg/mL for 0.12 ppm for 15 min, 167.8 ± 35.9 pg/mL for 0.24 ppm for 1 min, 209.2 ± 8.4 pg/mL for 0.24 ppm for 5 min, and 209.3 ± 14.3 pg/mL for 0.24 ppm for 15 min. Ozone significantly increased interleukin-8 concentrations compared to those for particulate matter dissolved in solution without ozone exposure and the solvent only (8.2 ± 0.9 pg/mL) in an ozone concentration-dependent manner. Collected particulate matter in solutions with or without bubbling through ozone had no effect on interleukin-6 production. The antioxidant -acetyl- -cysteine significantly inhibited the increases in interleukin-8 induced by solutions with particulate matter, regardless of ozone exposure. The reactive oxygen species concentration in solutions with collected particulate matter was not associated with ozone bubbling. Ozone may augment the production of interleukin-8 in response to ambient particulate matter by a mechanism unrelated to reactive oxygen species. These results support the epidemiological evidence for combined effects of ambient particulate matter and ozone on human health.