Bisphenol A-induced downregulation of murine macrophage activities in vitro and ex vivo.

Bisphenol A (BPA) is known to have detrimental effects on the reproductive system, but the toxicity of BPA on immune responses has not been systematically investigated. We investigated the effects of BPA exposure on the activities of murine peritoneal macrophages through evaluation of BPA-induced alteration of nitric oxide (NO) production, tumor necrosis factor-α (TNF-α) synthesis, and expression of co-stimulatory molecules B7. Macrophages were examined ex vivo from mice orally treated with various doses of BPA for 5 consecutive days per week for 4 weeks followed by culture for 2 or 4 days in the presence of lipopolysaccharides (LPS). Macrophages from naive mice were also stimulated with LPS ± BPA for 2 or 4 days. NO production was decreased with the in vitro exposure to 1, 10 and 100μM BPA. NO production was lower in the BPA-exposed mice than the control mice with all doses. In vitro, BPA suppressed TNF-α secretion with significant reduction at 10 and 100μM BPA. Similar findings were observed with the macrophages from the BPA-exposed mice. This study provides the substantial evidence on BPA-induced alteration in macrophage activity.