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)-1β 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-α and IL-1β secretion was significantly reduced in monocyte-derived macrophages. No difference was found in IL-10 secretion, whereas transforming growth factor-β 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-β 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.