- Vasoactive intestinal peptide induces pro-implantatory markers and modulates allomaternal response

L. FRACCAROLI, J. ALFIERI, V. ROCA, C. PEREZ LEIRÓS AND R. RAMHORST

Los Cocos Córdoba, Argentina

Congreso; Symposium on Maternal-Fetal Interaction Placenta-Research & Clinical; 2007

Human implantation occurs followed by a local proinflammatory and Th1-type response, subsequently controlled by a Th2-type response. Vasoactive intestinal peptide (VIP) is a potent anti-inflammatory agent with immunoregulatory properties, skewing the immune response to a Th2 pattern of cytokine production. Hence, we studied VIP-effects on tropohoblastic cells and in the maternal response to alloantigens. For that purpose, trophoblastic cells (Swan-71 an immortalized cytotrophoblast cells from first trimester) were cultured in the presence of VIP (10-7M) and after 24h cytokines (IL-6 and IL-10) secretion were quantified by ELISA and LIF expression by Western Blot. VIP significantly increase IL-6 secretion and LIF expression, however did not modulate the low levels of IL-10 observed (p<0.05 Student t test). Moreover, VIP increased thymidine uptake on trophoblastic cells after 72h of co-culture, either alone or co-cultured with PBMCs obtained from fertile women (p<0.05 Student t test). To study VIP effect on maternal alloresponse at systemic level, we performed co-cultures with PBMCs from fertile couples in the absence or presence of VIP, progesterone (10-5M) and maternal sera. After 5 days of culture thymidine uptake revealed that VIP supressed the allogenic response in the presence of progesterone, and the maternal sera did not modulate this effect. The same phenomena was observed when co-cultures were performed with PBMCs from patients with recurrent spontaneous abortion. The present data suggest that VIP induces throphoblast survival, contributing to a succesfull implantation in an adequate proinflammatory microenvironment.