congresos y reuniones científicas
Deficiencies in VIP levels during the feto-maternal dialogue conditioned the pregnancy outcome
FRACCAROLI L; LAROCCA L; CALAFAT M; ROCA V; PEREZ LEIROS C; RAMHORST R
Congreso; 29th Annual meeting of the American Society of Reproductive Immunology.; 2009
Successful embryo implantation occurs followed by a local pro-inflammatory and Th1 response, subsequently controlled by a Th2 response. VIP (vasoactive intestinal peptide) favors tolerance to fetal antigens displaying anti-inflammatory effects and promoting tolerogenic/Th2 responses. Since a potential exacerbated pro-inflammatory/Th1 response could be implicated into immunological abortion failures, we investigated whether VIP could control the initial pro-inflammatory response in patients with recurrent spontaneous abortions (RSA). We tested VIP effects on maternal PBMCs (from RSA and fertile women) after interaction with immortalized trophoblast cells (Swan 71) as representative model of feto-maternal dialogue; and we performed co-cultures of maternal and paternal PBMCs to test VIP effects on the systemic maternal alloresponse. After the interaction with trophoblast cells, RSA patients displayed low frequency of CD4+CD25+ FoxP3+ cells within maternal PBMCs and low levels of TGF-b (P < 0.05; Mann?Whitney test). VIP could not modulate the tolerogenic response in RSA patients as did in fertile women. However, during the trophoblast-RSA-PBMCs dialogue, VIP could modulate the initial inflammatory response in favor of a Th2 pattern response evidenced by a reduction in IL-6 and nitric oxide production while increased IL-10 and IL-5 secretion (P < 0.05; Student t test for each mediator). VIP effect on the cytokine-modulation balance was also accompanied with a significant reduction in TGF-b expression. Taken together these results suggest that VIP, produced by trophoblast cells under physiological conditions, favors a maternal tolerogenic response and could normalize the exacerbated-initial inflammatory response in RSA patients.