OBJECTIVE: To evaluate the effects of the immunosuppressant tacrolimus on rejection of a transplanted uterus and on uterine expression of markers of inflammation and implantation. DESIGN: Experimental study. SETTING: University laboratory. ANIMAL(S): Female rats. INTERVENTION(S): Uteri from brown Norway rats were transplanted to Lewis rats, receiving either tacrolimus or no treatment. Sham groups underwent either hemihysterectomy or tacrolimus treatment. MAIN OUTCOME MEASURE(S): Gross morphology, histology, density of T-lymphocytes by immunohistochemistry, and mRNA levels of interleukin (IL)-1α, leukemia inhibitory factor (LIF), galectin-1, CD200, IL-15, interferon-inducible protein-10 (IP-10), and nuclear factor-κB (NF-κB) at 14 days' post-transplantation. RESULT(S): Nontreated uterine grafts showed rejection with necrosis. Sham groups and the tacrolimus-treated transplanted group exhibited normal uterine morphology with low numbers of T-lymphocytes in all uteri except in two out of seven uteri of the tacrolimus-treated transplant group. Uteri of the nontreated transplanted group showed elevated mRNA expression of IL-1α and IP-10 and reduced galectin-1, compared with the tacrolimus-treated transplanted group. There was no difference between any groups concerning uterine expression of LIF, NF-κB, IL-15, and CD200. CONCLUSION(S): Tacrolimus monotherapy suppresses rejection of an allotransplanted uterus and normalizes the expression of IL-1α and IP-10 and prevents T-lymphocyte infiltration.
OBJECTIVE: To evaluate the effects of the immunosuppressant tacrolimus on rejection of a transplanted uterus and on uterine expression of markers of inflammation and implantation. DESIGN: Experimental study. SETTING: University laboratory. ANIMAL(S): Female rats. INTERVENTION(S): Uteri from brown Norway rats were transplanted to Lewis rats, receiving either tacrolimus or no treatment. Sham groups underwent either hemihysterectomy or tacrolimus treatment. MAIN OUTCOME MEASURE(S): Gross morphology, histology, density of T-lymphocytes by immunohistochemistry, and mRNA levels of interleukin (IL)-1α, leukemia inhibitory factor (LIF), galectin-1, CD200, IL-15, interferon-inducible protein-10 (IP-10), and nuclear factor-κB (NF-κB) at 14 days' post-transplantation. RESULT(S): Nontreated uterine grafts showed rejection with necrosis. Sham groups and the tacrolimus-treated transplanted group exhibited normal uterine morphology with low numbers of T-lymphocytes in all uteri except in two out of seven uteri of the tacrolimus-treated transplant group. Uteri of the nontreated transplanted group showed elevated mRNA expression of IL-1α and IP-10 and reduced galectin-1, compared with the tacrolimus-treated transplanted group. There was no difference between any groups concerning uterine expression of LIF, NF-κB, IL-15, and CD200. CONCLUSION(S): Tacrolimus monotherapy suppresses rejection of an allotransplanted uterus and normalizes the expression of IL-1α and IP-10 and prevents T-lymphocyte infiltration.