Lack of soluble TNF-receptors in women with recurrent spontaneous abortion and possibility for its correction.
OBJECTIVE
Tumor necrosis factor (TNF) and soluble TNF receptors (sTNF-Rs) system related with Th1 and Th2 and activity of NF-kappaB/IkappaB regulatory system. This study was designed to compare sTNF-R1 and sTNF-R2 production (shedding) and levels of late activated CD8+ T-lymphocytes in non-pregnant (n = 30) and pregnant (n = 20) normal women and non-pregnant (n = 20) and pregnant (n = 30) RSA women. Effects of progesterone (natural structure) injections in RSA women were studied.


METHODS
Levels of sTNF-R1, sTNF-R2, TNF in peripheral blood serum were detected by enzyme-linked immunosorbent assay. Lymphocyte subsets were estimated by multicolor flow cytometry. NK cell cytotoxic activity of peripheral blood lymphocytes (PBL) in whole blood against K562 targets was determined using Europium-release cytotoxicity assay. Mitogen-induced proliferative response of PBL to PHA-P, Con A and PWM were determined by standard 3H-thymidine incorporation assay.


RESULTS
Levels of soluble TNF-R1 and TNF-R2 in normal pregnancy were elevated when compared with non-pregnant normal women and pregnant RSA women. Levels of late activated CD8+ T-lymphocytes in normal pregnancy were decreased but no changes were detected in RSA women. After progesterone therapy (i.m. injections of 2.5% oil solution) in RSA women elevation of sTNF-R1 and sTNF-R2 to normal pregnancy ranges was observed. No changes in levels of late activated CD8+ T-lymphocytes after progesterone treatment were detected.


CONCLUSIONS
Elevation of levels of sTNF-R1, sTNF-R2 and decrease of late activated cytotoxic T-lymphocytes are pronounce markers of normal human pregnancy. In RSA women there are no elevation of sTNF-R1 and sTNF-R2 levels during pregnancy. This deficiency may be restored by progesterone treatment.
Chernyshov
Victor P
VP
Laboratory of Immunology, Institute of Pediatrics, Obstetrics and Gynecology, Academy of Medical Sciences, Kiev, Ukraine. chernyshov@ukr.net
Vodyanik
Maxim A
MA
Pisareva
Svetlana P
SP
D000026:Abortion, Habitual / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D000328:Adult; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D018655:Lymphocyte Count; D011374:Progesterone / Q000008:administration & dosage; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood* / Q000276:immunology; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology
D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011374:Progesterone