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 mononucle ar cells (PBMC) that causes interferon-gamma (IFN-gamma) production and enh ancement 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 polymet hylmethacrylate membrane (PMMA), and eight nondialyzed uremic patients (UR) . Ten healthy subjects constituted the control group (CON). PBMC were cultu red for 48 h with and without nonspecific mitogen stimulation. In unstimula ted 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 dialy sis (r = 0.69, P < 0.01). IL-12 release in CU remained unchanged under mito gen 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, respectiv ely; P < 0.05). IFN-gamma production was similar, in unstimulated condition s, 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 +/- 1 3.86, and 32.16 +/- 13.86 IU/ml, respectively; P < 0.01). These results dem onstrate that hemodialysis with CU induces monocyte activation with an enha nced 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. T he altered release of these cytokines could play a role in cell-mediated im munodeficiency of the uremic patients dialyzed with CU.