Vitamin E–loaded dialyzer resets PBMC-operated cytokine network in dialysis patients

Abstract

In hemodialysis patients the activity of stimulated Th1 lymphocytes is depressed, while Th2 cells are constitutively primed. Such phenomena may depend on monocyte activation and altered release of interleukin (IL)-12 and IL-18, which regulate Th cell differentiation. Reactive oxygen species (ROS) activate monocytes; therefore, a hemodialyzer with antioxidant activity would contrast ROS, prevent monocyte activation, reset IL-12 and IL-18 release, and restore Th1/Th2 balance. Ten patients on regular dialysis treatment (RDT) with cellulosic membrane (CM) were shifted to vitamin E-coated dialyzer (VE). During treatment with CM and after 3, 6, and 12 months of treatment with VE, peripheral blood mononuclear cells (PBMC) and purified CD4+ cells were isolated, and cultured, resting, mitogen-stimulated, and interferon gamma (IFNgamma), IL-4, IL-10, IL-12, and IL-18 release was measured. Vitamin E and A plasma levels and the effects of a single dialysis session on peripheral blood NO levels were assayed. The constitutive release of IL-4 and IL-10 by CD4+ cells was abated significantly by treatment with VE (nadir -77.8% and -55.3%, respectively, at 12 months). INFgamma release by mitogen-stimulated CD4+ recovered with VE (zenith +501% at 12 months). PBMC constitutive production of IL-12 and IL-18 was significantly reduced by VE (nadir at 12 months -64.7% and -51.3%, respectively). VE increased plasma levels of vitamins E and A. NO plasma levels fell after a single dialysis treatment with VE (-17%, P < 0.05) in contrast with CU (+27.1%, P < 0.05). The network of cytokines released by monocytes and Th cells is reset toward normality by treatment with vitamin E-coated dialyzer.