Ozone stimulates synthesis of inflammatory cytokines by alveolar macrophages in vitro.

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Abstract
Ozone (O-3) is one of the major irritant oxidant gases in photochemical smog. In the present study, the in vitro effect of low concentrations of O-3 (0.1 to 1 ppm) was evaluated on cell viability and cytokine secretion by alveolar macrophages (AM) from guinea pigs and healthy subjects. Cell injury was estimated immediately after O-3 exposure by evaluation of ATP cell content (measured by bioluminescence) and lactic dehydrogenase (LDH) release in the culture medium. No cytotoxic effect vias found: the ATP cell. content of both guinea pig AM and human AM did not significantly change after O-3 exposure and similarly the LDH release in the culture medium was unchanged. AM-derived cytokines, (tumor necrosis factor alpha [TNF alpha], interleukin-1 beta [IL-1 beta], interleukin-6 [IL-6], and interleukin-8 [IL-8]) were evaluated in AM supernatants. O-3 exposure was associated with a significant increase in cytokine secretion, with a peak value at 0.4 ppm O-3. The exposure of the guinea pig AM to 0.4 ppm O-3 for 60 min increased the IL-6 activity by 252 +/- 60% and TNF activity by 202 +/- 35%. The increase in monokine production by the human AM was 443 +/- 208% for TNF alpha 484 +/- 171% for IL-1 beta, 383 +/- 147% for IL-6, and 226 +/- 45% for IL-8 after a 60-min exposure to 0.4 ppm O-3. Lowest O-3 concentrations (0.1 and 0.2 ppm) only increased TNF alpha secretion. Shorter (30 min) or longer (120 min) exposure durations to 0.4 ppm O-3 were also associated with a significant increase in monokine production, suggesting that the effect of ozone on cytokine production did not depend on the exposure duration. The mRNA expression of TNF alpha: IL-1 beta, IL-6, and IL-8 was increased in human AM, whereas similar amounts of mRNA were detected in each sample. Our results demonstrate that low concentrations of O-3 increase the production of AM-derived monokines which may play a significant role in O-3-induced pulmonary inflammation and injury.