Effect of renal dialysis therapy modality on T cell cytokine production

INTRODUCTION: 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.