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).
Conclusion: 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.