Comparative in vitro Study of Different Peritoneal Dialysis Solutions on Cytokine Production by Peripheral Blood Mononuclear Cells

Abstract

Background/Aims: Peritoneal dialysis solutions (PDS), new and conventional, do not yet have a clinical biocompatibility profile. We aimed at a comparative laboratory profile based on the effect of PDS on peripheral blood mononuclear cell (PBMC) cytokine release. Method: PBMCs from 19 healthy volunteers were incubated at a concentration of 10⁶/ml in fresh PDS and control medium (RPMI 1640), and stimulated or not with 10μg/ml Escherichia coli lipopolysaccharide. The tested PDS were glucose/lactate 1.5 and 4.25%, glucose/pyruvate 1.0 and 4.0%, icodextrin and amino acid solutions. The initial incubation in culture flasks for 15 min was followed by 1:1 dilution with RPMI and by additional incubation for 22 h as a ‘recovery period’. At the end, the supernatants were tested for cytokines IL-6 and TNFα by ELISA. Results: The hypertonic glucose solutions, irrespective of the buffer, had the most adverse effect on PBMC cytokine release. The icodextrin and amino acid solutions seemed close to the isotonic glucose PDS. The substitution of pyruvate for lactate buffer seemed to offer an advantage only for the hypertonic glucose-based solutions. Conclusions: Icodextrin and amino acid solutions seem to offer an advantage only compared to hypertonic glucose PDS.

Addition of Alanyl-Glutamine to Dialysis Fluid Restores Peritoneal Cellular Stress Responses – A First-In-Man Trial

“…Functionally, exposure to AlaGln-supplemented PDF significantly enhanced ex-vivo release of TNF-α and IL-6 upon LPS-stimulation, a biomarker which has previously been adapted to discriminate between effects of different PDF on peritoneal host defenses [ 9 , 10 , 38 , 39 ]. Our trial confirmed marked suppression of LPS-stimulated TNF-α and IL-6 release by a standard PDF and demonstrated comparable effects of addition of AlaGln to PDF as were previously described by improving biocompatibility of PDF [ 9 , 10 , 38 , 39 ]. Using various systemic biomarkers, smoldering inflammation [ 55 ] and Gln deficiency were shown to suppress immune competence during sepsis or following major trauma or surgery [ 44 , 56 , 57 ].…”

“…PDF effluent interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis factor alpha (TNF-α) were measured by Immulite® system (Siemens, Vienna, Austria) or by Bio-Plex bead array (Bio-Rad, Hercules, CA). Lipopolysaccharide (LPS)-stimulated cytokine release was carried out as described [ 38 , 39 ] with minor modifications. Human peripheral blood mononuclear cells (PBMCs) were exposed at 37°C either to 4 h PET effluents mixed 1:1 with fresh PDF or to pure effluents for 4 h. LPS (from E .…”

Treg/Th17 imbalance is associated with cardiovascular complications in uremic patients undergoing maintenance hemodialysis

“…Activation of inflammatory response centered on the excretion of cytokines is closely associated with cardiovascular complications in uremic cases (5,6), particularly by T cells (7). IL-10-producing CD4 + CD25 + Foxp3 + regulatory T cells (Tregs) contribute to anti-inflammatory response (8), while the IL-17-induced T-helper cells (Th17s) exhibit a pro-inflammatory role (9).…”