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Strong additive effect of 1,25-dihydroxycholecalciferol and cyclosporine A but not tacrolimus in rat lung allotransplantation.
Eur J Cardiothorac Surg. 2003 Aug; 24(2):196-200; discussion 200.EJ

Abstract

OBJECTIVES

1,25-Dihydroxycholecalciferol (calcitriol, vitamin D3) has immunosuppressive properties. This study evaluates the effect of calcitriol in combination with either cyclosporine A or tacrolimus on acute lung allograft rejection in a rat model of unilateral left lung allotransplantation.

METHODS

Unilateral left lung transplantation was performed in male rats (Brown-Norway to Fischer F344, 200-250 g body weight). For immunosuppression, the following subtherapeutic doses were used: calcitriol 0.5 microg/kg/day, cyclosporine A 2.5 mg/kg/day i.p., and tacrolimus 40 microg/kg i.m. Five groups (n = 5) were analyzed: cyclosporine A; cyclosporine A and calcitriol; calcitriol; tacrolimus and calcitriol; and tacrolimus. The injections were performed for 5 days starting from the day of transplantation. Recipients were sacrificed on day 5 post-transplant. The contralateral right main bronchus and pulmonary artery were occluded for 5 min and blood was drawn for blood gas analysis. The grafts were excised, fixed in formaline and embedded in paraffin. Histological evaluation was done in blinded fashion (ISHLT 1999/rank scale). The mean and standard error of the mean (PaO2) or the median and range (rejection grading) are given. ANOVA followed by planned comparison for the PaO2 and Kruskal-Wallis ANOVA for rejection grading were applied, p < 0.05 considered significant.

RESULTS

Arterial PaO2 on day 5 was very low in animals treated with subtherapeutic dosages of either cyclosporine A (48 +/- 10 mmHg), calcitriol (51 +/- 3) or tacrolimus (86 +/- 22). Combined treatment with cyclosporine A and calcitriol revealed a significant improvement (248 +/- 78; p < 0.05 vs. other groups), whereas the combination of tacrolimus with calcitriol did not reveal any benefit (65 +/- 9). Rejection grading with these subtherapeutic doses did not show any significant difference between groups.

CONCLUSIONS

Our data indicate that cyclosporine A, but not tacrolimus, has a strong additive effect with calcitriol on acute rat lung allograft rejection.

Authors+Show Affiliations

Division of General Thoracic Surgery, University Hospital Berne, CH-3010, Berne, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

12895607

Citation

Stammberger, Uz, et al. "Strong Additive Effect of 1,25-dihydroxycholecalciferol and Cyclosporine a but Not Tacrolimus in Rat Lung Allotransplantation." European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery, vol. 24, no. 2, 2003, pp. 196-200; discussion 200.
Stammberger U, Kubisa B, Gugger M, et al. Strong additive effect of 1,25-dihydroxycholecalciferol and cyclosporine A but not tacrolimus in rat lung allotransplantation. Eur J Cardiothorac Surg. 2003;24(2):196-200; discussion 200.
Stammberger, U., Kubisa, B., Gugger, M., Ayuni, E., Claudio, R., Grodzki, T., & Schmid, R. A. (2003). Strong additive effect of 1,25-dihydroxycholecalciferol and cyclosporine A but not tacrolimus in rat lung allotransplantation. European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery, 24(2), 196-200; discussion 200.
Stammberger U, et al. Strong Additive Effect of 1,25-dihydroxycholecalciferol and Cyclosporine a but Not Tacrolimus in Rat Lung Allotransplantation. Eur J Cardiothorac Surg. 2003;24(2):196-200; discussion 200. PubMed PMID: 12895607.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Strong additive effect of 1,25-dihydroxycholecalciferol and cyclosporine A but not tacrolimus in rat lung allotransplantation. AU - Stammberger,Uz, AU - Kubisa,Bartosz, AU - Gugger,Matthias, AU - Ayuni,Erick, AU - Claudio,Redaelli, AU - Grodzki,Tomasz, AU - Schmid,Ralph Alexander, PY - 2003/8/5/pubmed PY - 2003/12/3/medline PY - 2003/8/5/entrez SP - 196-200; discussion 200 JF - European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery JO - Eur J Cardiothorac Surg VL - 24 IS - 2 N2 - OBJECTIVES: 1,25-Dihydroxycholecalciferol (calcitriol, vitamin D3) has immunosuppressive properties. This study evaluates the effect of calcitriol in combination with either cyclosporine A or tacrolimus on acute lung allograft rejection in a rat model of unilateral left lung allotransplantation. METHODS: Unilateral left lung transplantation was performed in male rats (Brown-Norway to Fischer F344, 200-250 g body weight). For immunosuppression, the following subtherapeutic doses were used: calcitriol 0.5 microg/kg/day, cyclosporine A 2.5 mg/kg/day i.p., and tacrolimus 40 microg/kg i.m. Five groups (n = 5) were analyzed: cyclosporine A; cyclosporine A and calcitriol; calcitriol; tacrolimus and calcitriol; and tacrolimus. The injections were performed for 5 days starting from the day of transplantation. Recipients were sacrificed on day 5 post-transplant. The contralateral right main bronchus and pulmonary artery were occluded for 5 min and blood was drawn for blood gas analysis. The grafts were excised, fixed in formaline and embedded in paraffin. Histological evaluation was done in blinded fashion (ISHLT 1999/rank scale). The mean and standard error of the mean (PaO2) or the median and range (rejection grading) are given. ANOVA followed by planned comparison for the PaO2 and Kruskal-Wallis ANOVA for rejection grading were applied, p < 0.05 considered significant. RESULTS: Arterial PaO2 on day 5 was very low in animals treated with subtherapeutic dosages of either cyclosporine A (48 +/- 10 mmHg), calcitriol (51 +/- 3) or tacrolimus (86 +/- 22). Combined treatment with cyclosporine A and calcitriol revealed a significant improvement (248 +/- 78; p < 0.05 vs. other groups), whereas the combination of tacrolimus with calcitriol did not reveal any benefit (65 +/- 9). Rejection grading with these subtherapeutic doses did not show any significant difference between groups. CONCLUSIONS: Our data indicate that cyclosporine A, but not tacrolimus, has a strong additive effect with calcitriol on acute rat lung allograft rejection. SN - 1010-7940 UR - https://www.unboundmedicine.com/medline/citation/12895607/Strong_additive_effect_of_125_dihydroxycholecalciferol_and_cyclosporine_A_but_not_tacrolimus_in_rat_lung_allotransplantation_ L2 - https://academic.oup.com/ejcts/article-lookup/doi/10.1016/s1010-7940(03)00300-2 DB - PRIME DP - Unbound Medicine ER -