Murine fetal resorption and experimental pre-eclampsia are induced by both excessive Th1 and Th2 activation.
It has been proposed that immune responses in mammalian normal pregnancy are Th2-like, thereby protecting the fetus and placenta from being rejected. Administration of exogenous Th1 cytokines into pregnant mice is reported to induce feto-placental resorption. However, the effects of exogenous Th2 cytokines and Th2 directed responses in pregnant animals have not been well studied. In this study, we examined IL-4 and IL-12, which play decisive roles in the development of Th2 and Th1 responses, respectively, in the induction of fetal resorption and development of experimental pre-eclampsia. Transfer of either IL-4 and/or IL-12 stimulated splenocytes from BALB/C virgin female mice into BALB/C pregnant mice mated with either C57BL/6 or BALB/C male mice resulted in fetal resorption and glomerular nephritis associated with hypertension and proteinuria. In mice treated with IL-12 stimulated splenocytes, fatty liver degeneration associated with bile retention was observed. These results indicate that both excessive Th1 and Th2 activation contribute to the development of fetal resorption and pre-eclampsia, but that Th1 is critical to the development of liver degeneration.
Hayakawa
S
S
Department of Obstetrics and Gynaecology, Nihon University School of Medicine, Tokyo, Japan. satoshih@med.nihon-u.ac.jp
Fujikawa
T
T
Fukuoka
H
H
Chisima
F
F
Karasaki-Suzuki
M
M
Ohkoshi
E
E
Ohi
H
H
Kiyoshi Fujii
T
T
Tochigi
M
M
Satoh
K
K
Shimizu
T
T
Nishinarita
S
S
Nemoto
N
N
Sakurai
I
I
D019264:Adoptive Transfer; D000818:Animals; D005260:Female; D005327:Fetal Resorption / Q000276:immunology*; D006973:Hypertension; D018664:Interleukin-12 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000473:pathology; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D009393:Nephritis; D011225:Pre-Eclampsia / Q000276:immunology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000276:immunology*; D011507:Proteinuria; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells; D018418:Th2 Cells
D018664:Interleukin-12; D015847:Interleukin-4