Vol. 9, No 2, 2002 pp. 166 - 170
UC 618.2+615.2
EFFECTS OF INDOMETACIN ON ALLOGENIC AND
SYNGENIC PREGNANCY
Zoran Poptrajković1,
Stevo Najman2, Borislav Kamenov3,
Vojin Savić4, Ivan Bubanović5
1Clinic of Gynecology
and Obstetretics, KC, Niš
2Institute of
Biology, Faculty of Medicine, Niš
3Children's Internal
Clinic, KC, Nis
4Institute of
Biomedical Research, Faculty of Medicine, Niš
5Department of
Gynecology and Obstetretics, Health Center Gnjilane, Yugoslavia
Summary. Factors of making and keeping immunotolerance in pregnancy
mainly affect immunocompetent cells by immunosuppressive factors or moving
of Th1/Th2 balance in favour of Th2 response. Errors made in making and
keeping immunotolerance in pregnancy can lead to clinic entities such as
resorption of fetoplacental unit, miscarriage and reduced placental and
fetal weight. Besides, production of sex steroids in the yellow body of
gravidity and later in the fetoplacental unit depends on the factors such
as prostaglandins and cytokines. The significance of paternal and maternal
MHC (in)compatibility of rats for the number of embryos, percentage of
embryos in resorption, placental and fetal weight and the level of serum
steroids were tested in our experiment. Specimens taken for this investigation
were syngene Sprague Doley (SD) and Wistar (W). The rats of SD and W lineage
were treated by indometacin of 2.1-2.8 mg/kg daily by giving them drinking
water in the period of 6-18 day of pregnancy. Stimulation of Th1 response
by indometacin in allogenic pregnancy led to resorption of 56% embryos
while the rate of resorption in the control group of W rats was 12%. Syngene
SD animals treated by indometacin did not show a significantly higher rate
of embryos in resorption (8.14%) than the ones in the control group (5.13%)
Acceleration of Th1 response by indometacin led to activation of decidual
CTL and NK cells as well as to intensified expression of MHC antigens on
the cells of trophoblast. In allogenic pregnancy this resulted in the increased
resorption of embryos, while in SYNGENIC pregnancy acceleration of Th1
response did not result in increased resorption of embryos. Besides, indometacin
leads to the significant fall of the level of serum progesterone and oestradiol
notwithstanding the MHC compatibility of pregnancy However, the level of
serum progesterone in W rats treated by indometacin is significantly lower
than in SD rats also treated by indometacin. This result shows the possibility
of greater damage of trophoblast in MHC incompatible pregnancies under
the influence of indometacin or greater activities of cytokine of Th1 group,
which inhibits synthesis of sex steroids.
Key words: Pregnancy, indometacin, progesterone, oestradiol,
prostaglandin, immunomodulation,
Th1 and Th2 response
EFEKAT INDOMETACINA NA ALOGENU I SINGENU
TRUDNOĆU
Kratak sadržaj: Faktori uspostavljanja i ordržavanja gravidarne
imunotolerancije uglavnom deluju direk-tno imunosupresivno na imunokompetentne
ćelije ili na pomeranje Th1/Th2 balansa u korist Th2 odgovora. Greške u
uspostavljanju i održavanju gravidarne imunotolerancije dovode od kliničkih
entiteta kao što su resorpcija feto-placentne jedinice, spontani pobačaj,
smanjena placentna i fetalna masa. Osim toga, produkcija polnih ster-oida
u žutom telu trudnoće, a kasnije u feto-placentnoj jedinici je zavisna
od faktora kao što su prostaglandini i cito-kini. U našem eksperimentu
je ispitivan značaj paternalne i maternalne MHC (in)kompatibilnosti pacova
na brojnost plodova, procenat plodova u resorpciji, placentnu i fetalnu
masu i nivo serumskih steroida. Kao eksperimentalni model su poslužili
singeni Sprague Doley (SD) i alogeni Wistar (W) pacovi. Pacovi soja SD
i W su tretirani indo-matacinom 2,1-2,8 mg/kg dnevno kroz pijaću vodu od
6. do 18. dana trudnoće. Stimulacija Th1 odgovora indo-metacinom je u alogenoj
trudnoći dovela do resorpcije 56% plodova dok je stopa resorpcije u kontrolnoj
grupi W pacova bila 12,5%. Singene SD životinje tretirane indometacinom
nisu pokazale značajno veću stopu plodova u re-sorpciji (8,14%) od kontrolne
grupe (5,13%). Akceleracija Th1 odgovora indometacinom je dovela do aktivacije
de-cidualnih Tc i NK ćelija, kao i do pojačane ekspresije MHC antigena
na ćelijama trofoblasta. U slučaju alogene trudnoće, ovo je rezultovalo
povećanom resorpcijom plodova, dok u singenoj trudnoći akceleracija Th1
odgovora nije rezultovala povećanjem resorpcije plodova. Osim toga, indometacin
dovodi do značajnog pada nivoa serumskog progesterona i estradiola bez
obzira na MHC kompatibilnost trudnoće. Međutim, nivo serumskog progesterona
kod W pacova tretiranih indometacinom je značajno niži nego kod SD pacova
takođe tretiranih indometacinom, što ukazuje na mogućnost većeg oštećenja
trofoblasta u MHC inkopatibilnim trudnoćama pod uticajem indo-metacina
ili veće aktivnosti citokina Th1 grupe koji inhibišu sintezu polnih steroida.
Ključne reči: Trudnoća, indometacin, progesteron, estradiol,
imunomodulacija, Th1 i Th2 odgovor
