Uterine rejection after allogeneic uterus transplantation in the rat is effectively suppressed by tacrolimus

Capsule:
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.

Authors:
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

Abstract:

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.

Animals:
Female rats.

Interventions:
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.

Results:
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.

Conclusions:
Tacrolimus monotherapy suppresses rejection of an allotransplanted uterus and normalizes the expression of IL-1α and IP-10 and prevents T-lymphocyte infiltration.

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