Uterine rejection after allogeneic uterus transplantation in the rat is effectively suppressed by tacrolimus
In a rat model of allogeneic uterus transplantation, the immunosuppressant tacrolimus effectively prevented uterine rejection, and expression patterns of inflammation-/implantation-related proteins of the uteri were similar to those of controls.
Shamima N. Akhi, M.D., Cesar Diaz-Garcia, M.D., Randa R. El-Akouri, M.D., Ph.D., Caiza A. Wranning, Ph.D., Johan Mölne, M.D., Ph.D., Mats Brännström, M.D., Ph.D.
Volume 99, Issue 3, Pages 862-870, 1 March 2013
To evaluate the effects of the immunosuppressant tacrolimus on rejection of a transplanted uterus and on uterine expression of markers of inflammation and implantation.
Uteri from Brown Norway rats were transplanted to Lewis rats, receiving either tacrolimus or no treatment. Sham groups underwent either only laparotomy or tacrolimus treatment.
Main Outcome Measures:
Gross morphology, histology, density of Tlymphocytes 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.
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 2 out of 7 uteri of the tacrolimus-treated transplant group. Uteri of the non-treated transplanted group showed elevated mRNA expression of IL-1α and IP-10 and reduced galectin-1, compared to the tacrolimus-treated transplanted group. There was no difference between any groups concerning uterine expression of LIF, NF-κB, IL-15 and CD200.
Tacrolimus monotherapy suppresses rejection of an allotransplanted uterus and normalizes the expression of IL-1α and IP-10 and prevents T-lymphocyte infiltration.