Quantitative flow cytometry shows activation of the TNF-α system but not of the IL-2 system at the single cell level in renal replacement therapy

Abstract

Background. Immunological dysfunction in patients on haemodialysis may be related to imbalanced cytokine systems, such as tumour necrosis factor (TNF)-α and interleukin (IL)-2. Despite activation of these systems, haemodialysis patients show high susceptibility for infections and malignancies, and have a poor immunological reaction to T-cell-dependent antigens, like hepatitis B vaccination. In this study we have determined the activation status of the two different cytokine systems, at the single cell level, using quantitative flow cytometry. Methods. Using fluorescein isothiocyanate- or phycoerythrin-conjugated antibodies directed against TNF-R2 (CD120b), IL-2Rα (CD25) and IL-2Rβ (CD122), we measured the expression of these receptors at the single cell level in order to determine the level of activation of monocytes and T-lymphocytes. Results. Significantly higher expression of the TNF-α receptor, TNF-R2, was present on both monocytes and T-lymphocytes in patients on renal replacement therapy (RRT) compared with pre-dialysis chronic renal failure (CRF) patients and controls, indicating activation of the TNF-α system. In contrast, IL-2R expression was comparable in all groups studied, which may reflect a non-activated state of the IL-2 system. Conclusions. The present study illustrates an activated state of the TNF-α system in patients on RRT, at the single cell level, while the IL-2 system seems to be unaffected. These findings support the hypothesis that the interaction between the TNF-α and IL-2 cytokine systems is disturbed.