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Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
Published on: November 8, 2015
Tacrolimus Modulates Peripheral Blood NK Cell Subsets and IL-17/IL-10 Ratio in Women With Recurrent Implantation
Marzieh Zamaniyan1,2, Sepideh Peivandi1,2, Imaneh Ahmadi1
1Department of Obstetrics and Gynecology, IVF Ward, Faculty of Medicine Imam Khomeini Hospital, Mazandaran University of Medical Sciences Sari Iran.
Purpose:
Recurrent implantation failure (RIF) is linked to immune dysregulation. Although tacrolimus has shown clinical benefits in RIF, its immunological mechanisms remain unclear. We assessed its effects on peripheral blood NK cell subsets and cytokine profiles.
Methods:
Thirty women with RIF and 30 fertile controls were enrolled. Patients received oral tacrolimus (3 mg/day) before embryo transfer until pregnancy testing. NK cell subsets and IL-17/IL-10 expression were assessed by flow cytometry and real-time PCR before and after treatment.
Results:
At baseline, RIF patients showed higher NK cell-associated subsets and increased IL-17/IL-10 ratio compared with controls (CD16+: p = 0.019; CD56+: p < 0.0001; CD16+CD56+: p < 0.0001; IL-17/IL-10 ratio: p < 0.0001). Following tacrolimus, CD16+ (p = 0.011), CD56+ (p = 0.001), and CD16+CD56+ (p = 0.001) NK cells, as well as IL-17 levels (p < 0.0001) and the IL-17/IL-10 ratio (p = 0.0036), were significantly reduced, whereas IL-10 expression remained unchanged (p = 0.406). Greater reductions in the IL-17/IL-10 ratio were associated with clinical pregnancy (p = 0.048), suggesting predictive value for implantation success.
Conclusions:
Tacrolimus modulated immune pathways by reducing pro-inflammatory NK subsets and shifting the IL-17/IL-10 balance toward tolerance, supporting its potential as targeted immunotherapy in selected patients.
