Real-time PCR assessment of Interleukin (IL)-12, IL-18 and IL-15 levels in the endometrium of patients with a history of repeated IVF-ET failure: A new way to explore cytokine defects in early pregnancy?

Abstract

ObjectiveTo document in the endometrium the correlations between the Interleukin (IL)-12,-15 and -18 mRNA and the correlations between the cytokines levels, the vascular status and the endometrial NK cell count in a context of recurrent implantation failure .DesignWe explored the endometrium of women who failed to become pregnant after repeated IVF-ET (IF group) (n=38) and fertile control subjects (n=8).Materials and methodsAn ultrasonic evaluation and an endometrial biopsy was performed during in day 21 of a non conceptional cycle. The main measurements were the: uterine artery Doppler, the count of uterine CD56bright cells (uNK) / field, the IL-18 and IL-12 immunostaining and the normalized cytokines quantification by real time PCR of the levels of mRNA for the IL-12 family gene products (IL-12p40, IL-12p35, EBI3, IL-23), the IL-18 system (IL-18, IL-18R, IL18BP) and IL-15.ResultsFertile and infertile patients were significantly different for their uterine artery Doppler and the CD56 bright cells count. The mean uterine artery pulsatility index was significantly negatively correlated to the IL-18/actin ratio suggesting a defect of the cytokine dependent vascular remodeling pathway. The number of uterine CD56 bright cells was significantly correlated to the IL-15/Actin and IL-18/ IL-18BP ratios. Thus IL-18 and IL-15 seems to be involved in the local recruitment and the activation of uNK cells. IL-18 was itself correlated with the IL-15 and IL-12 suggesting a local control of uNK cells activation.ConclusionThe assessment of the tripod IL-12/15/18 allows to distinct immune-related mechanisms involved in the broader context of inadequate uterine receptivity. ObjectiveTo document in the endometrium the correlations between the Interleukin (IL)-12,-15 and -18 mRNA and the correlations between the cytokines levels, the vascular status and the endometrial NK cell count in a context of recurrent implantation failure . To document in the endometrium the correlations between the Interleukin (IL)-12,-15 and -18 mRNA and the correlations between the cytokines levels, the vascular status and the endometrial NK cell count in a context of recurrent implantation failure . DesignWe explored the endometrium of women who failed to become pregnant after repeated IVF-ET (IF group) (n=38) and fertile control subjects (n=8). We explored the endometrium of women who failed to become pregnant after repeated IVF-ET (IF group) (n=38) and fertile control subjects (n=8). Materials and methodsAn ultrasonic evaluation and an endometrial biopsy was performed during in day 21 of a non conceptional cycle. The main measurements were the: uterine artery Doppler, the count of uterine CD56bright cells (uNK) / field, the IL-18 and IL-12 immunostaining and the normalized cytokines quantification by real time PCR of the levels of mRNA for the IL-12 family gene products (IL-12p40, IL-12p35, EBI3, IL-23), the IL-18 system (IL-18, IL-18R, IL18BP) and IL-15. An ultrasonic evaluation and an endometrial biopsy was performed during in day 21 of a non conceptional cycle. The main measurements were the: uterine artery Doppler, the count of uterine CD56bright cells (uNK) / field, the IL-18 and IL-12 immunostaining and the normalized cytokines quantification by real time PCR of the levels of mRNA for the IL-12 family gene products (IL-12p40, IL-12p35, EBI3, IL-23), the IL-18 system (IL-18, IL-18R, IL18BP) and IL-15. ResultsFertile and infertile patients were significantly different for their uterine artery Doppler and the CD56 bright cells count. The mean uterine artery pulsatility index was significantly negatively correlated to the IL-18/actin ratio suggesting a defect of the cytokine dependent vascular remodeling pathway. The number of uterine CD56 bright cells was significantly correlated to the IL-15/Actin and IL-18/ IL-18BP ratios. Thus IL-18 and IL-15 seems to be involved in the local recruitment and the activation of uNK cells. IL-18 was itself correlated with the IL-15 and IL-12 suggesting a local control of uNK cells activation. Fertile and infertile patients were significantly different for their uterine artery Doppler and the CD56 bright cells count. The mean uterine artery pulsatility index was significantly negatively correlated to the IL-18/actin ratio suggesting a defect of the cytokine dependent vascular remodeling pathway. The number of uterine CD56 bright cells was significantly correlated to the IL-15/Actin and IL-18/ IL-18BP ratios. Thus IL-18 and IL-15 seems to be involved in the local recruitment and the activation of uNK cells. IL-18 was itself correlated with the IL-15 and IL-12 suggesting a local control of uNK cells activation. ConclusionThe assessment of the tripod IL-12/15/18 allows to distinct immune-related mechanisms involved in the broader context of inadequate uterine receptivity. The assessment of the tripod IL-12/15/18 allows to distinct immune-related mechanisms involved in the broader context of inadequate uterine receptivity.