Low-flux hemodialysis suppresses interferon-gamma production: the possible role of beta2-microglobulin.
Interferon-gamma (IFN-gamma) is required for the acquired immune response involving maturation and activation of antigen-presenting cells (APC); both IFN-gamma production and activation of APC are impaired in ESRD patients on low-flux hemodialysis (HD). High levels of uremic toxins including beta2-microglobulin (beta2M) are thought to play a role in immunosuppression.


METHODS
To test this hypothesis, we conducted an A-B-A crossover study to examine the influence of high-flux HD (A) versus low-flux HD (B) in ESRD patients (n = 14) using biocompatible synthetic dialyzer membranes (Polyamix(R), Gambro, Hechingen, Germany) and ultrafiltered bicarbonate-buffered dialysis fluid. Each study period lasted 6 months and at the end of each period, Kt/V urea, plasma levels of albumin, C-reactive protein (CRP) and beta2M were determined. In addition, production of IFN-gamma induced by heat-killed Staphylococcus epidermidis (Staph epi) was performed in whole blood cultures.


RESULTS
Kt/V urea (mean +/- SEM) was 1.45 +/- 0.06 in Period A, 1.36 +/- 0.07* in Period B, and 1.51 +/- 0.07 in Period A' (*p < 0.01). beta2M resting levels increased from 26.6 +/- 1.42 mg/l in Period A to 34.7 +/- 2.30* mg/l in Period B, and decreased to 21.6 +/- 1.07 mg/l at the end of Period A' (*p < 0.0001). Albumin and CRP levels did not differ significantly. Staph epi-induced IFN-gamma production was 1.2 +/- 0.39 ng/1,000 PBMC at the end of Period A, 0.34 +/- 0.10 ng/1,000 PBMC* in Period B, and 2.71 +/- 0.67 ng/1,000 PBMC at the end of Period A' (*p < 0.05). There was an inverse correlation between b2M levels and whole blood IFN-gamma production (R2 = 0.26).


CONCLUSIONS
High levels of uremic toxins such as beta2M suppress IFN-gamma production in ESRD patients under low-flux HD. High-flux HD reduces beta2M levels by 30% and improves IFN-gamma production suggesting an improved cellular immune response in ESRD patients.
Lonnemann
G
G
Group Practice Nephrology/Dialysis, Langenhagen, University of Colorado Denver, Aurora, CO, USA. Lonnemann@eickenhof-dialyse.de
Bahlmann
F H
FH
Freise
J
J
Hertel
B
B
Dinarello
C A
CA
D000328:Adult; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D006435:Renal Dialysis / Q000379:methods*; D001613:beta 2-Microglobulin / Q000502:physiology*
D001613:beta 2-Microglobulin; D007371:Interferon-gamma