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1,25-Dihydroxycholecalciferol with low-calcium diet reduces acute rejection in rat lung allotransplantation

Kubisa, Bartosz ; Stammberger, Uz ; Gugger, Mathias ; Uduehi, Aima Norma ; Grodzki, Tomasz ; Schmid, Ralph Alexander

In: European Journal of Cardio-Thoracic Surgery, 2012, vol. 42, no. 5, p. 871-877

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    Title
    • 1,25-Dihydroxycholecalciferol with low-calcium diet reduces acute rejection in rat lung allotransplantation
    Author
    • Kubisa, Bartosz. Division of General Thoracic Surgery, University Hospital, Berne, Switzerland
    • Stammberger, Uz. Division of General Thoracic Surgery, University Hospital, Berne, Switzerland
    • Gugger, Mathias. Department of Pathology, University Hospital, Berne, Switzerland
    • Uduehi, Aima Norma. Division of General Thoracic Surgery, University Hospital, Berne, Switzerland
    • Grodzki, Tomasz. Clinical Department of Thoracic Surgery, Pomeranian Medical University, Szczecin-Zdunowo, Poland
    • Schmid, Ralph Alexander. Division of General Thoracic Surgery, University Hospital, Berne, Switzerland
    Document Type
    • Postprint
    Language
    • English
    Published in
    • European Journal of Cardio-Thoracic Surgery, 2012, vol. 42, no. 5, p. 871-877. Oxford University Press
    Other Version
    OAI-PMH Identifier
    • oai:doc.rero.ch:295570
    Summary
    OBJECTIVES The effect of 1,25-dihydroxycholecalciferol (calcitriol, vitamin D3) with a low-calcium diet on the acute lung allograft rejection in a rat unilateral left lung transplantation model was evaluated. METHODS Three transplantation groups were studied (n=5, male Brown-Norway to Fischer F344, 235±15g body weight): calcitriol and low-calcium diet, low-calcium diet and normal diet. Calcitriol (4μg/kg/day) was injected intraperitoneally for 5 days, starting from the day of transplantation. In addition, two non-transplantation groups were compared: (n=3, Brown-Norway) to measure the level of cytokines, and Fischer F344 receiving calcitriol and a low-calcium diet to measure the serum calcium level. The recipients of transplantation were killed on Day 5 post-transplant. The contralateral right main bronchus and the pulmonary artery were occluded for 5min and blood was drawn for the blood gas analysis, and the grafts were assessed for histology (International Society for Heart and Lung Transplantation 1996/rank scale). Lung levels of interleukin (IL)-2, IL-6, IL-12 and tumour necrosis factor-α (TNF-α) were assessed within the calcitriol and low-calcium diet, low-calcium diet and Brown-Norway groups. The serum calcium level was assessed in the Fischer F344 group. An analysis of variance with Tukey's post hoc test was used to compare the arterial blood oxygen pressure and the lung cytokine expression between groups. A non-parametric Kruskal-Wallis test followed by the Siegel and Castellan post hoc test was used to assess the differences between the groups according to the lung graft rejection grading. Student's paired t-test was used to compare the serum calcium level. RESULTS The arterial PaO2 was significantly higher in the calcitriol and the low-calcium diet groups when compared with low-calcium diet or normal diet groups (356±72mmHg; P<0.05 vs other groups). The arterial and bronchial rejection observed in calcitriol and low-calcium diet group was significantly milder than in the low-calcium diet or normal diet groups (A1-2, B1-2; P<0.05 vs other groups). IL-2 and IL-6 levels were significantly higher in low-calcium diet vs calcitriol and low-calcium diet and Brown-Norway groups. IL-12 and TNF-α did not differ among the groups. There was no significant difference in serum calcium level before and after the treatment in the Fischer F344 group. CONCLUSIONS Calcitriol with a low-calcium diet treatment improves lung function, reduces lung allograft acute rejection, decreases IL-2 and IL-6 allograft expression and does not change the serum calcium level significantly