Vasoactive intestinal peptide induces pro-implantatory

FRACCAROLI L; ALFIERI J; ROCA V; PEREZ LEIROS C; RAMHORST R

Córdoba, Argentina,

Congreso; III Latin-American Symposium on Maternal-Fetal Interaction; 2007

Placenta – Research & Clinical,

Human implantation is followed by a local proinflammatory and a Th1-type response,and is subsequently controlled by a Th2-type response. Vasoactive intestinal peptide(VIP) is a potent anti-inflammatory agent with immunoregulatory properties, skewingthe immune response to a Th2 pattern of cytokine production. Hence, we studied VIPeffectson trophoblastic cells and in the maternal response to alloantigens. For thatpurpose, trophoblastic cells (Swan-71, an immortalized cytotrophoblast cells from firsttrimester) were cultured in the presence of VIP (10-7M) and after 24h, cytokine (IL-6and IL-10) secretion was quantified by ELISA and LIF expression by Western Blot.VIP significantly increased IL-6 secretion and LIF expression, but did not modulatethe low levels of the observed IL-10 (p<0.05 Student t test). Moreover, VIP increasedthymidine uptake on trophoblastic cells after 72h of co-culture, either alone or co-culturedwith PBMCs obtained from fertile women (p<0.05 Student t test). To study VIPeffect on maternal alloresponse at systemic level, we performed co-cultures with PBMCsfrom fertile couples in the absence or presence of VIP, progesterone (10-5M) and maternalsera. After 5 days of culture thymidine uptake revealed that VIP suppressed the allogenicresponse in the presence of progesterone, and the maternal sera did not modulate thiseffect. The same phenomenon was observed when co-cultures were performed withPBMCs from patients with recurrent spontaneous abortions. The present data suggestthat VIP induces trophoblast survival, contributing to a successful implantation in anadequate proinflammatory microenvironment.