The Measurement of Cytokine Production Capacity during Dialysis - a New Dynamic Method for the Evaluation of Biocompatibility?

Abstract

The activation of monocytes and other immunocompetent cells during hemodialysis can be attributed to their contact with immunogenic structures such as membranes, blood lines, and endotoxins. The simple measurement of cytokines in blood cannot completely describe the whole dimension of this event. Stimulation of monocytes and other immunocompetent cells in whole blood with lipopolysaccharides (LPS) for IL-6 and phytohemagglutinine (PHA) for TNF at the start and end of dialysis may make it possible to better analyze cellular response during dialysis. Ten healthy volunteers and 10 patients suffering from chronic renal failure were tested with the commercial whole-blood stimulation assays “Dynamix”-IL-6-DIA and -TNF-alpha-DIA (Biosource Diagnostics, Ratingen, Germany). Then 24 patients undergoing hemodialysis with hemophane (n=12) and polyamide (n=12) membranes were examined before and after dialysis treatment. The unpaired Wilcoxon t- test was used for statistical analysis. Healthy volunteers and patients with chronic renal failure showed no statistical differences in concentrations of TNF-alpha and IL-6 before or after whole blood stimulation (WBS). In comparison to patients with chronic renal failure, pre-WBS concentrations of both cytokines (p<0.034) were increased in patients of each membrane group before dialysis. After whole blood stimulation, no differences were observed. At the end of dialysis treatment, the pre- and post-WBS IL-6 values were both significantly higher in the hemophane group (p=0.049 and p=0.0038, respectively) TNF-alpha concentrations were unchanged. No significant differences in the polyamide group were found between the start and end of treatment for either cytokine. A comparison of these membrane groups showed that only the pre-WBS IL-6 concentration in the hemophane group was elevated (p=0.022) after dialysis. In conclusion, the presence of uremia alone could not influence the cytokine production and release capacity. In our patients, dialysis elevated pre-WBS concentrations of TNF-alpha and IL-6, and increased IL-6 release from immunocompetent cells after whole blood stimulation in the hemophane group. The use of polyamide membranes decreased the action of monocytes and other immunocompetent cells, but could not completely prevent this phenomenon. The whole blood stimulation assays for measurement of TNF-alpha and IL-6 may represent a new, dynamic method for evaluating biocompatibility.