Effect of renal dialysis therapy modality on T cell cytokine production.
BACKGROUND
Dialysis has been associated with acute changes in the complement activation status, granulocyte markers, macrophage function, T cell activation and the release of pro-inflammatory cytokines. The most common analysis of cytokine production in patients on dialysis has focused on the changes in monokines (particularly IL-1 and TNF alpha), however it is becoming clear that T cell cytokines play a major role in the impaired lymphocyte function of dialysis patients.


METHODS
To assess the effect of dialysis modality on T cell function we analysed the ability of T cells within peripheral blood mononuclear cell populations (PBMC) to produce cytokines after mitogen (phorbol-12-myristate-13-acetate; PMA and lonomycin; I) stimulation in patients on peritoneal dialysis (PD) compared to low flux haemodialysis (HD) and normal individuals (controls).


RESULTS
In control PBMC, PMA + I stimulation significantly increased the percentage of CD3+ cells expressing IL-2, IFN gamma, TNF alpha, IL-4 and IL-10, as expected. However, although mitogen stimulation significantly enhanced the percentage of the classical Th1 cytokines (IL-2, IFN gamma and TNF alpha) in the low flux HD PBMC, it had no effect on CD3+ IL-2 or CD3+ TNF alpha producing cells in the PD group. In contrast, the percentage of T cells producing Th2 cytokines (IL-4 and IL-10) could not be consistently enhanced by mitogen in either dialysis group.


CONCLUSIONS
We suggest that PD alters the ability of T cells to produce cytokines, possibly by causing an 'exhaustion' of the Th1 cells, thereby preventing cells to produce cytokine on ex vivo stimulation. Furthermore, since T cells from both low flux HD and PD groups could not be induced to produce Th2 cytokines we suggest that uraemia or dialysis per se inhibits T cells from producing Th2 cytokines.
The Anthony Nolan Bone Marrow Trust, The Royal Free Hospital, London, UK.
A
A
Zamauskaite
I
I
Perez-Cruz
M M
MM
Yaqoob
J A
JA
Madrigal
S B
SB
Cohen
D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D005260:Female; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis; D012016:Reference Values; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate