Asunto(s)
Ciclosporina/uso terapéutico , Citocinas/efectos de los fármacos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Riñón/efectos de los fármacos , Tacrolimus/uso terapéutico , Células TH1/efectos de los fármacos , Células Th2/efectos de los fármacos , Citocinas/metabolismo , Femenino , Humanos , Riñón/metabolismo , Masculino , Células TH1/inmunología , Células Th2/inmunologíaRESUMEN
We have analysed the frequency of cytokine-producing T cells in different dialysis groups (haemodialysis; HD and peritoneal dialysis; PD) over time. Although we saw no difference in type 1 cytokine production (IL-2 and IFN-gamma) in either dialysis group, there was a clear increase in the percentage of T cells spontaneously producing the type 02 cytokines in the PD group (IL-4, r = 0.558, P < 0.05; IL-10, r = 0.527, p < 0.05). Our patient group was carefully selected to include patients with an ongoing autoimmune disease, insulin dependent diabetes mellitus (IDDM) (DN group) and chronic glomerulonephritis (GN), which are common reasons of end stage renal failure. As expected there was no increase in the spontaneous production of either IL-4 or IL-10 in either disease group with patients undergoing HD treatment. However, there was a clear correlation with the frequency of T cells producing IL-4 (r = 0.755, P < 0.05) and IL-10 (r = 0.725, P < 0.05) and time on dialysis in the PD patients with DN, but not those with GN. Much work has suggested that the pathogenesis of IDDM is associated with a Th1 dominated response. We show here that this response is skewed towards a Th2 response after long term treatment with PD. This work demonstrates that the immunological effects of different dialysis modalities on patients with different diseases vary. This may go some way to explain why certain patient groups have more complications with different dialysis modalities.
Asunto(s)
Recuento de Linfocito CD4 , Nefropatías Diabéticas/inmunología , Fallo Renal Crónico/inmunología , Diálisis Peritoneal , Células Th2 , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/terapia , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/terapia , Nefropatías Diabéticas/terapia , Glomerulonefritis/complicaciones , Glomerulonefritis/inmunología , Glomerulonefritis/terapia , Humanos , Interleucina-10/metabolismo , Interleucina-4/metabolismo , Fallo Renal Crónico/etiología , Fallo Renal Crónico/terapia , Diálisis Renal , Células Th2/metabolismo , Factores de TiempoRESUMEN
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.