Hemodialysis-related lymphomononuclear release of interleukin-12 in patients with end-stage renal disease.
Interleukin-12 (IL-12) is a cytokine produced by peripheral blood mononuclear cells (PBMC) that causes interferon-gamma (IFN-gamma) production and enhancement of cell-mediated cytotoxicity. To clarify the role of hemodialysis biocompatibility on IL-12 production and uremic immunodeficiency, we have studied the IL-12 and IFN-gamma release by PBMC harvested from 12 patients dialyzed with cuprophan membrane (CU), eight patients dialyzed with polymethylmethacrylate membrane (PMMA), and eight nondialyzed uremic patients (UR). Ten healthy subjects constituted the control group (CON). PBMC were cultured for 48 h with and without nonspecific mitogen stimulation. In unstimulated conditions, CU showed an IL-12 PBMC production higher than CON, UR, and PMMA (46.67 +/- 30.13 versus 2.56 +/- 1.38, 6.16 +/- 7.09, and 4.62 +/- 4.76 pg/ml, respectively; P < 0.01). IL-12 production was correlated with C3a concentration measured at the outlet of hemodialyzer after 15 min of dialysis (r = 0.69, P < 0.01). IL-12 release in CU remained unchanged under mitogen stimulation (44.34 +/- 23.86 pg/ml) and was lower than in CON, UR, and PMMA (66.0 +/- 12.41, 68.37 +/- 25.78, and 67.75 +/- 22.61 pg/ml, respectively; P < 0.05). IFN-gamma production was similar, in unstimulated conditions, in all groups. Under stimulation, IFN-gamma release was lower in CU (13.42 +/- 12.04 IU/ml) than in CON, UR, and PMMA (51.84 +/- 30.74, 32.16 +/- 13.86, and 32.16 +/- 13.86 IU/ml, respectively; P < 0.01). These results demonstrate that hemodialysis with CU induces monocyte activation with an enhanced release of IL-12. On the contrary, stimulated PBMC production of both IL-12 and IFN-gamma is lower in these patients than in CON, UR, and PMMA. The altered release of these cytokines could play a role in cell-mediated immunodeficiency of the uremic patients dialyzed with CU.