TGF-BETA(2) AND PGE(2) IN RABBIT BLASTOCOELIC FLUID CAN MODULATE GM-CSF PRODUCTION BY HUMAN-LYMPHOCYTES

PROBLEM: During normal pregnancy, major changes occur in the productio n of Th2/Th1 cytokines at the fete-maternal interface. Th2 cytokines s uch as interleukin-4 (IL-4) or interleukin-10 (IL-10) are predominantl y produced locally in the uterine and placental tissues, whereas the p roduction of Th1 cytokines such as tumor necrosis factor alpha (TNF-al pha) and interferon gamma (IFN-gamma) are decreased. Because these mod ulations might be induced by the embryo, the current study was carried out to test the effect of rabbit blastocoelic fluid on the production of Th2/Th1 cytokines by lymphocytes, and to investigate the possible implication of transforming growth factor beta(2) (TGF-beta(2)) prosta glandin E-2 (PGE(2)) as modulators of the production of these cytokine s. METHOD OF STUDY: Human peripheral blood lymphocytes (PBL) were cult ured along with Concanavalin A (Con A), and rabbit blastocoelic fluid was collected on day 12 of gestation (BF d-12). Concentrations of cyto kines in culture media were determined by enzyme-linked immunoadsorben t assay (ELISA). RESULTS: Addition of BF d-12 in the culture medium in duced a strong inhibition of IL-2, TNF-alpha, IL-10, and granulocyte-m acrophage colony-stimulating factor (GM-CSF) production. However, an i nitial pretreatment of the lymphocytes with BF d-12, followed by a Con A stimulation, led to a marked increase in GM-CSF production, whereas IL-2, TNF-alpha, and IL-10 secretions were inhibited. It was also dem onstrated, for the first time, that a pretreatment of the lymphocytes with TGF-beta(2) and PGE(2) increased GM-CSF production to the same le vel reached after the addition of BF d-12. Furthermore, removal of TGF -beta(2) and PGE(2) from BF d-12 by affinity chromatography reduced th e effect of BF d-12 on GM-CSF production. CONCLUSIONS: Taken together, these findings suggest that the embryo, in modulating harmful and ben eficial cytokine production locally, plays an active role in its prote ction against maternal immune cellular assault. These results also emp hasize the importance of growth factors for successfully maintaining p regnancy.