Constant, but not pulsed calcitriol suppresses hemodialysis patients' antigen-induced lymphocyte proliferation.
OBJECTIVE
In vitro constant calcitriol [1,25-(OH)(2)D(3)] inhibits healthy individuals' T lymphocyte proliferation at supraphysiological concentrations. In contrast, among hemodialysis patients, intravenous 1,25-(OH)(2)D(3) pulse therapy of secondary hyperparathyroidism has been shown to be even immunostimulatory. We studied the effect of in vitro constant and intermittent 1, 25-(OH)(2)D(3) on lymphocyte antigen response of hemodialysis patients.


METHODS
Twelve hemodialysis patients' peripheral blood mononuclear cells were stimulated with purified protein derivative of tuberculin (12.5, 25 and 50 mg/l) or tetanus toxoid (TT; 1,000, 5, 000 and 10,000 Lf/l, limit of flocculation) for 7 days. Constant 1, 25-(OH)(2)D(3) was added to all cultures at concentrations of 0, 10(-10) or 0.25 x 10(-9) mol/l (0, 42 and 105 ng/l) and to half of the cultures additionally as a 0.75 x 10(-9) mmol/l (315-ng/l) pulse on the 5th culture day.


RESULTS
TT-induced lymphocyte proliferation was statistically related to a constant 1,25-(OH)(2)D(3) concentration (p = 0.001, analysis of variance). With constant 1, 25-(OH)(2)D(3) concentrations of 0, 42 and 105 ng/l, the TT-induced responses were 1.53, 1.44 and 1.40 log cpm, respectively (mean of TT concentrations). The responses of the (additionally) pulse-treated cells [1.65, 1.50 and 1.40 log cpm; concentrations of constant 1, 25-(OH)(2)D(3) as above] were similar to those of the nonpulsed cells. Thus constant, but not pulsed 1,25-(OH)(2)D(3) decreased the TT responses. On the purified protein derivative of tuberculin response, neither constant nor pulsed 1,25-(OH)(2)D(3) had any significant effect.


CONCLUSIONS
The decline of TT response with constant 1,25-(OH)(2)D(3) corresponds with findings on immunosuppressive action of 1,25-(OH)(2)D(3) in previous studies done on normal subjects' cells. This was not seen with intermittently applied 1,25-(OH)(2)D(3). These results support the previous concept that intermittent 1,25(OH)(2)D(3) therapy is not immunosuppressive in hemodialysis patients.
Hannula
P M
PM
Department of Medicine, Tampere University Hospital, Tampere, Finland. paivi.hannula@uta.fi
Antonen
J A
JA
Saha
H H
HH
Koivisto
A M
AM
Krohn
K J
KJ
Pasternack
A I
AI
D000328:Adult; D000368:Aged; D000941:Antigens / Q000494:pharmacology; D002117:Calcitriol / Q000008:administration & dosage / Q000627:therapeutic use*; D002478:Cells, Cultured; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D006435:Renal Dialysis; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013745:Tetanus Toxoid / Q000494:pharmacology*; D014373:Tuberculin / Q000494:pharmacology*
D000941:Antigens; D013745:Tetanus Toxoid; D014373:Tuberculin; D002117:Calcitriol