Mitochondrial disruption in isolated human monocytes: an underlying mechanism for cadmium-induced immunotoxicity.

Abstract

Cadmium (Cd) is an immunotoxic metal frequently found in the environment. The in vitro study undertaken here evaluated the immunotoxic effects of Cd in isolated human peripheral blood monocytes (hPBM). The results of the studies of exposures to varying doses of Cd (0, 0.1, 1, 10, and 100 µM, as cadmium dichloride [CdCl₂]) for 3, 6, 12, 24, 48, and 72 hr showed the test agent was cytotoxic to the cells in time- and concentration-related manners. Thereafter, using only those doses found to not cause extreme cell lethality a 48-hr period, the impact of 0.1 or 1 µM CdCl₂ on the cells was evaluated. Functionally, CdCl₂ treatment led to time- and concentration-related decreases in hPBM phagocytic activities as well as in the ability of the cells to form/release cytokines (including tumor necrosis factor [TNF]-α and interleukin [IL]-6 and -8). The CdCl₂ also led to significantly decreased ATP production (in part, via inhibition of mitochondrial complexes I and III) as well as in mitochondrial membrane potentials (MMP) and oxygen consumption rates (OCR; associated with parallel increases in cell lactate production) in the cells. In addition, CdCl₂ treatment resulted in significant increases in mitochondrial membrane fluidity (MMF) and cell unsaturated fatty acid content. Based on the results here, one might conclude that some of the effects that arose during the CdCl₂-induced dysfunction of the isolated hPBM (i.e. changes phagocytic activity, cytokine formation/secretion) could have evolved secondary to CdCl₂-induced disruptions of hPBM cell bioenergetics - an effect that itself was a culmination of an overall toxicity from CdCl₂ upon the mitochondria within these cells.