INTERLEUKIN-6, INTERLEUKIN-8 AND MONOCYTE CHEMOTACTIC PEPTIDE-1 GENE-EXPRESSION AND PROTEIN-SYNTHESIS ARE INDEPENDENTLY MODULATED BY HEMODIALYSIS MEMBRANES

Background Uremia produces a wide range of abnormalities of the immune system. Blood-membrane interaction in hemodialysis results in activat ion and severe dysfunction of peripheral blood mononuclear cells (PBMC ). However, the question of whether the use of different dialytic memb ranes may improve PBMC dysfunctions remains unanswered. Methods. To ad dress this issue, the spontaneous interleukin (IL)-6, IL-8 and monocyt e chemotactic peptide-1 (MCP-1) gene expression and protein release we re studied in PBMC isolated from 7 healthy subjects, 8 uremic patients on conservative therapy and 8 uremic patients undergoing subsequent o ne month periods of hemodialysis with cuprophan (CU) and high-flux non complement activating membranes, polymethylmethacrylate (PMMA) and pol yamide (PA). At the end of each period of treatment, PBMC were harvest ed at the beginning (T0) and after 180 minutes of dialysis (T180), and then were cultured in complete medium. IL-6, IL-8 and MCP-1 mRNA expr ession were studied by RT-PCR. In addition, MCP-1 gene expression was evaluated also by in situ hybridization. Cytokines released in the sup ernatant were measured by ELISA. Results. Compared to the control grou p, PBMC from uremic patients on conservative therapy and treated by CU showed a clear reduction in the cytokine release, while PMMA and PA m embranes were able to normalize IL-6, IL-8 and MCP-1 protein concentra tion, which had been reduced by CU treatment. Interestingly, at TO, mR NA expression for all three cytokines was increased in the patients tr eated by CU, when compared to the control group and the uremic patient s on conservative therapy. A further up-regulation was observed at T18 0. PMMA and PA treatment, despite increasing the cytokine secretion, s ignificantly reduced the dialysis-induced cytokine gene expression. Co nclusion. PBMC exposure to CU membranes results in cytokine mRNA overe xpression associated with a paradoxically reduced protein release. In contrast, long-term hemodialysis with synthetic high-flux membranes re duces IL-6, IL-8 and MCP-1 gene expression and improves the ability of PBMC to secrete these cytokines. The reduced cytokine secretion durin g bioincompatible dialysis may reflect a PBMC adaptation that protects uremic patients against the inflammatory effects of persistent cytoki ne release.