| pubmed-article:8123758 | pubmed:abstractText | Acute or chronic exposure to cadmium (Cd) causes severe organ damages with the infiltration of leukocytes, neutrophils in particular occurring in the acute phase. Interleukin-8 (IL-8), a novel neutrophil chemotactic and activating cytokine, is produced by various types of cells in response to a wide variety of inflammatory stimuli. The administration of an antibody against IL-8 has been shown to inhibit neutrophil infiltration in several animal models, indicating a causal relationship between IL-8 and neutrophil infiltration. Hence, in this study we investigated whether Cd induced IL-8 production in human peripheral blood mononuclear cells (PBMC). Cd, over a wide range of concentrations, did induce human PBMC to produce large amounts of bioactive IL-8, the maximal induction being observed at 10(-4) M. The production was inhibited specifically by a metal chelating agent, ethylenediaminetetraacetic acid (EDTA). Steady level of IL-8 mRNA increased within 30 min after the addition of Cd and reached a maximal level at 2 h, decreasing thereafter. A protein synthesis inhibitor, cycloheximide, failed to inhibit IL-8 mRNA accumulation, indicating that new protein synthesis was not required for IL-8 mRNA induction. Concomitantly with the induction of IL-8, within 10 min Cd generated reactive oxygen intermediates (ROI) in human PBMC. A radical scavenger, N-acetyl-L-cysteine (NAC), inhibited both IL-8 production and the generation of ROI, implying the possible involvement of ROI in IL-8 production. This notion was also supported by our findings that a superoxide generating agent, paraquat, induced IL-8 production in human PBMC and that NAC blocked this paraquat-induced IL-8 production. | lld:pubmed |
