Quantitative flow cytometry shows activation of the TNF-alpha system but not of the IL-2 system at the single cell level in renal replacement therapy.
BACKGROUND
Immunological dysfunction in patients on haemodialysis may be related to imbalanced cytokine systems, such as tumour necrosis factor (TNF)-alpha 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-2Ralpha (CD25) and IL-2Rbeta (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-alpha 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-alpha 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-alpha 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-alpha and IL-2 cytokine systems is disturbed.
van Riemsdijk-Van Overbeeke
I C
IC
Department of Internal Medicine, University Hospital Rotterdam-Dijkzigt, The Netherlands.
Baan
C C
CC
Knoop
C J
CJ
Loonen
E H
EH
Zietse
R
R
Weimar
W
W
D000328:Adult; D015703:Antigens, CD / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002138:Calibration; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000276:immunology* / Q000628:therapy; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D009426:Netherlands; D010531:Peritoneal Dialysis, Continuous Ambulatory; D020033:Protein Isoforms / Q000097:blood; D044469:Racial Groups; D015375:Receptors, Interleukin-2 / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D047889:Receptors, Tumor Necrosis Factor, Type II; D012016:Reference Values; D006435:Renal Dialysis; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D015415:Biomarkers; D020033:Protein Isoforms; D015375:Receptors, Interleukin-2; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II