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


METHODS
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.


RESULTS
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).


CONCLUSIONS
The network of cytokines released by monocytes and Th cells is reset toward normality by treatment with vitamin E-coated dialyzer.
Libetta
Carmelo
C
Unit of Nephrology, Dialysis and Transplantation, IRCCS Policlinico San Matteo and University, Pavia, Italy. clibettapv@hotmail.com
Zucchi
Manuela
M
Gori
Elena
E
Sepe
Vincenzo
V
Galli
Francesco
F
Meloni
Federica
F
Milanesi
Fabio
F
Dal Canton
Antonio
A
D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D001672:Biocompatible Materials; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002482:Cellulose / Q000031:analogs & derivatives*; D020099:Coated Materials, Biocompatible; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008297:Male; D008567:Membranes, Artificial; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000097:blood; D006435:Renal Dialysis / Q000295:instrumentation*; D019233:Retreatment; D013997:Time Factors; D014801:Vitamin A / Q000097:blood; D014810:Vitamin E / Q000097:blood
D000975:Antioxidants; D001672:Biocompatible Materials; D020099:Coated Materials, Biocompatible; D016207:Cytokines; D007378:Interleukins; D008567:Membranes, Artificial; D014801:Vitamin A; D014810:Vitamin E; D009569:Nitric Oxide; C005062:acetylcellulose; D007371:Interferon-gamma; D002482:Cellulose