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대한생식의학회지 제24권 제3호 2010년
반복 유산환자의 말초혈액 단핵구와 태반항원을 체외 공동 배양시 세포 매개 면역반응에 프로게스테론이 미치는 영향
삼성 제일병원 산부인과, 습관성 유산 크리닉;하버드 의과대학 산부인과, 습관성 유산 크리닉;
최범채;;,
The Effects of Progesterone on Cell Mediated Immunity to Trophoblast in Woman with Recurrent Pregnancy Loss
Choi, Bum-Chae;Hill, Joseph A.;
Recurrent Pregnancy Loss Clinic, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Samsung Cheil Hospital & Women's HealthCare Center;Recurrent Pregnancy Loss Clinic, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School;
Progesterone is necessary for successful pregnancy and had immunosuppressive properties. Peripheral blood mononuclear cells (PBMC) from many women with unexplained recurrent spontaneous abortion responded to trophoblast extract in vitro by prolifertion and releasing soluble, heat-labile factors that are toxic to mouse embryos (embryotoxic factors). Accumulating evidence suggests that T Helper (Th)-1 type immunity to trophoblast is correlated with embryotoxic factor production and is associated with pregnancy loss, while Th2-type immunity is associated with successful gestation. The objective of this study was to determine whether progesterone can inhibit Th1-type cytokine secretion (IFN-${\gamma}$, TNF-${\alpha}$) by trophoblast-activated peripheral blood mononuclear cells from 23 nonpregnant women (age 25-35) with unexplained recurrent abortion (median 5, range 3 to 15)who otherwise produce embryotoxic factors in response to trophoblast. We also determined whether progesterone affected Th2-type cytokines (IL-4, IL-10) in this system in vitro and if IL-10 (1,500 pg/mL) could inhibit Th1-type immunity to trophoblast. IFN-${\gamma}$ was detected in 17 of 23 (74%) trophoblast stimulated PBMC culture supernatants ($77.94{\pm}23.79$ pg/mL) containing embryotoxic activity. TNF-${\alpha}$ was detected in 19 (83%) of these same supernatants ($703.15{\pm}131.36$ pg/mL). In contrast, none of the supernatants contained detectable levels of IL-4 or IL-10. Progesterone ($10^{-5}$, $10^{-7}$, $10^{-9}$M) inhibited Th1-type immunity in a dose dependent manner, but had no effect on Th2-type cytokine secretion. The inhibitory effects of progesterone were abrogated with RU486, but did not affect Th2-type cytokine secretion in trophoblast-activated cell cultures. IL-10, like progesterone also inhibited Th1-type cytokine secretion but had no effect on Th2-type cytokines. These data suggest that therapies designed to suppress Th1-type cytokine secretion in women with recurrent abortion who have evidence of Th1-type immunity to trophoblast may be efficacious in preventing pregnancy loss and should be tested in appropriately designed clinical trials.
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