Cadmium (Cd) is a contaminant in cigarette smoke and may play an important role in the pathogenesis of smoking-related emphysema. It is reported that repeated Cd exposure causes emphysema after neutrophil infiltration in the rat lung. Interleukin-8 (IL-8) is a major neutrophil chemotactic factor commonly involved in a variety of pulmonary disorders including emphysema. The aim of this study is to elucidate the effect of Cd on IL-8 production of alveolar epithelial type II cells, using the A549 cell line. We used 1–100 mM of cadmium chloride (CdCl2) to stimulate the cells for a 48 h period. IL-8 production (2957 ± 137 pg/mL) without any cytotoxic effect was observed in the cell supernatants after 24 h exposure to 50 mM CdCl2. The Cd-removed supernatant caused neutrophil chemotaxis and was inhibited by the anti-IL-8 antibody.
Cd-induced IL-8 was inhibited by EDTA, and the inhibition was blocked by copper (II) chloride. The addition of anti-interleukin-1b or tumor necrosis factor-a antibodies did not diminish IL-8 release induced by Cd. These results suggest that Cd increases the production of IL-8 without any cytotoxic effect in alveolar epithelial cells, which may be an important factor in the developmental process of cigarette smoking-related emphysema.
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