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      Constant, but Not Pulsed Calcitriol Suppresses Hemodialysis Patients’ Antigen-Induced Lymphocyte Proliferation

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          Background/Aims: In vitro constant calcitriol [1,25-(OH)<sub>2</sub>D<sub>3</sub>] inhibits healthy individuals’ T lymphocyte proliferation at supraphysiological concentrations. In contrast, among hemodialysis patients, intravenous 1,25-(OH)<sub>2</sub>D<sub>3</sub> 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)<sub>2</sub>D<sub>3</sub> 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)<sub>2</sub>D<sub>3</sub> was added to all cultures at concentrations of 0, 10<sup>–10</sup> or 0.25 × 10<sup>–9</sup> mol/l (0, 42 and 105 ng/l) and to half of the cultures additionally as a 0.75 × 10<sup>–9</sup> 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)<sub>2</sub>D<sub>3</sub> concentration (p = 0.001, analysis of variance). With constant 1,25-(OH)<sub>2</sub>D<sub>3</sub> 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)<sub>2</sub>D<sub>3</sub> as above] were similar to those of the nonpulsed cells. Thus constant, but not pulsed 1,25-(OH)<sub>2</sub>D<sub>3</sub> decreased the TT responses. On the purified protein derivative of tuberculin response, neither constant nor pulsed 1,25-(OH)<sub>2</sub>D<sub>3</sub> had any significant effect. Conclusions: The decline of TT response with constant 1,25-(OH)<sub>2</sub>D<sub>3</sub> corresponds with findings on immunosuppressive action of 1,25-(OH)<sub>2</sub>D<sub>3</sub> in previous studies done on normal subjects’ cells. This was not seen with intermittently applied 1,25-(OH)<sub>2</sub>D<sub>3</sub>. These results support the previous concept that intermittent 1,25(OH)<sub>2</sub>D<sub>3</sub> therapy is not immunosuppressive in hemodialysis patients.

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          Most cited references 3

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          The immunobiology ofvitamin D

           R.W. Baldwin (1988)
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            Immunological properties of vitamin D analogues and metabolites.

             Lise Binderup (1992)
            This commentary has attempted to describe some of the new aspects of our knowledge of the immunological properties of 1 alpha,25(OH)2D3, the physiologically active metabolite of vitamin D3, and its new analogues. These analogues will, in the future, serve as tools to increase our understanding of the role of vitamin D in immunobiology, not only in basal research but also, hopefully, in the therapy of immune-mediated diseases.
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              Vitamin D and the immune system

               Edward Amento (1987)

                Author and article information

                S. Karger AG
                October 2000
                22 September 2000
                : 86
                : 2
                : 139-144
                aDepartment of Medicine, Tampere University Hospital, Tampere, bTampere School of Public Health, and cInstitute of Medical Technology, University of Tampere, Finland
                45732 Nephron 2000;86:139–144@5L}@4E}
                © 2000 S. Karger AG, Basel

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                Figures: 2, Tables: 3, References: 36, Pages: 6
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