Lead treatment in vitro at early developmental stage of bone marrow-derived macrophages enhances NO production through IL-1β and IL-6 but not TNF-α

Abstract Lead (Pb 2+ ) is known to decrease or block nitric oxide (NO) production by mature macrophages (mφ). Bone marrow cells were treated with various doses of lead in vitro and the morphological and functional changes were observed. Bone marrow cells were treated with various doses of lead (1, 10, 20 and 50 μM) at the start of culture with mφ growth factor (CSF-1), and after 6–7 days of culture, the resultant mφ (bone marrow-derived mφ, BMDM) showed decreased NO production. Unexpectedly, BMDM from the lowest does of lead treatment (1.0 μM) showed increased NO production. The increased NO production was due to increased expression of the iNOS gene and concurrent enhanced transcript levels of proinflammatory cytokines such as IL-1β and IL-6, but not TNF-α. Lead treatment on mature BMDM showed decreased NO production in a dose-dependent manner. These results suggest that a low dose of lead affects developmental characteristics of BMDM through different proinflammatory cytokines, and the lead effects on precursor cells of mφ and mature mφ are different.