Estradiol enhances murine cardiac allograft rejection under cyclosporin and can be antagonized by the antiestrogen tamoxifen.
BACKGROUND
An increased incidence of acute rejection episodes in female heart transplant recipients has been reported in experimental and clinical studies. However, the exact mechanisms of gender-specific differences in alloreactivity are not completely understood.


METHODS
C57BL/10 (H-2b) hearts were transplanted into C3H/He (H-2 k) recipients. Four gender combinations were used to test the influence of donor and recipient sex on graft survival. Recipients were treated with CsA, 17beta-estradiol and/or tamoxifen. Additionally mice were ovariectomized prior to transplantation.


RESULTS
Treated with CsA, allograft survival in female recipients was 9.16+/-0.41 days as compared with 15.16+/-1.72 days in males. Estradiol administration and oophorectomy had a significant impact on allograft survival in male and female mice under CsA treatment. Tamoxifen combined with CsA significantly prolonged graft survival in female recipients (13.16+/-1.16 days) as compared with CsA treatment alone (9.16+/-0.41 days).


CONCLUSIONS
Female mice show earlier rejection episodes and a shorter graft survival than males. For the first time, tamoxifen has been shown to have a beneficial effect on heart allograft survival in female recipients.
Department of Hepatobiliary Surgery, Beijing 309 Hospital, Peoples Republic of China.
Yiping
Y
Zou
Wolfgang
W
Steurer
Günther
G
Klima
Peter
P
Obrist
Raimund
R
Margreiter
Gerald
G
Brandacher
D000818:Animals; D016572:Cyclosporine / Q000627:therapeutic use*; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology*; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D012727:Sex Characteristics; D013629:Tamoxifen / Q000627:therapeutic use*
D004965:Estrogen Antagonists; D007166:Immunosuppressive Agents; D013629:Tamoxifen; D004958:Estradiol; D016572:Cyclosporine