Production of inflammatory molecules in peripheral blood mononuclear cells from severely glucose-6-phosphate dehydrogenase-deficient subjects

Abstract: Objective: We have previously demonstrated that Mediterranean glucose-6-phosphate dehydrogenase (G6PD)- deficient peripheral blood mononuclear cells ( PBMC) respond to mitogenic stimuli with a reduced cholesterol synthesis and growth. In the present study, we have investigated the release of inflammatory molecules by PBMC following a mitogenic stimulus, as well as the transformation to foam cells of monocyte-derived macrophages from severely G6PD-deficient and normal subjects. Methods and Results: PBMC from G6PD-deficient subjects produced interleukin ( IL)-1 beta and IL-6 to a lower extent compared with normal subjects. 5-Hydroxyeicosatetraenoic acid, a primary product of 5-lipoxygenase, was slightly decreased. Tumour necrosis factor-alpha and IL-1 beta secretion was significantly reduced in monocyte-derived macrophages. No difference was found in IL-1 beta secretion, whereas transforming growth factor-beta was invariably found to be significantly higher in G6PD-deficient cells. In cells incubated with acetylated low- density lipoprotein, cholesterol esterification and its storage in lipid droplets were lower than in normal G6PD cells. Conclusions: We conclude that by reducing the secretion of inflammatory molecules by PBMC and increasing the secretion of transforming growth factor-beta and the capability of monocyte- derived macrophages to accumulate lipid droplets and convert into foam cells, G6PD deficiency may confer a partial protection against atherosclerosis leading to the reduced risk of cardiovascular diseases reported in G6PD- deficient subjects.