Produzione linfomonocitaria di interleuchina 12 in pazienti uremici cronici

Patients with end-stage renal disease present symptoms of acquired defects in the cell-mediated immune response. IL-12 is a heterodimeric cytokine of 79 kDa (p70) with several biological effects on T helper type 1 and natural killer cells, including induction of interferon Γ production and enhancement of cell-mediated cytotoxicity. In order to evaluate the role of this cytokine in uremic immune deficiency, we investigated the IL-12 (p70, ELISA assay) release by peripheral blood mononuclear cells (PBMCs) harvested from 13 chronic hemodialyzed patients (EDE), 6 undialyzed uremic patients (IRC), and 6 healthy control subjects (CON). PBMCs, obtained by gradient density centrifugation with Ficoll Hypaque, were cultured for 48 h in supplemented Iscove medium with and without nonspecific mitogens (lipopolysaccharide, 10 ng/ml). In EDE, IL-12 production from PBMCs was increased in comparison to the control and IRC values (59.1 ± 39.9 vs 6.8 ± 7.3 and 18.8 ± 11.9 pg/ml respectively, p <0.05). By contrast, when PBMCs collected from EDE were stimulated by 24-hour LPS incubation the production of IL-12 was significantly lower than that observed in CON and IRC (54.7 ± 23.6 vs 180.4 ± 98.8 and 102.0 ± 60.9 pg/ml, respectively, p <0.05). In conclusion, our results demonstrate that hemodialysis treatment induces monocyte activation with an enhanced spontaneous release of IL-12; by contrast, PBMC production of IL-12 after mitogen incubation is lower in hemodialysis patients with respect to CON and IRC patients. This altered release of these cytokines may play a role in the cell-mediated immunodeficiency of chronic hemodialysis patients.