title: [Reproductive hormones in the control of Th1/Th2 cytokine balance].
abstract: Individual and combined effects of chorionic gonadotropin (CG), estradiol, and progesterone on the production of IFNgamma and IL-4 by human peripheral blood lymphocytes was studied in vitro together with certain intracellular mechanisms underlying the hormonal effects. High CG dose (100 IU/ml) proved to significantly decrease IFNgamma level in the T cell culture supernatant, although this effect was not observed at the background of steroid hormones. In contrast, progesterone (100 ng/ml) increased IFNgamma production by activated T lymphocytes but proved inefficient in a physiological combination with CG and estradiol. IL-4 production was almost doubled by all studied hormones and their combinations, which considerably decreased the IFNgamma/IL-4 ratio in the culture. Inhibition analysis employing blockers of cAMP-dependent protein kinase (H-89) and L-type calcium channels (verapamil) as well as an antagonist of progesterone nuclear receptors (RU-486) demonstrated that the inhibitory (for IFNgamma) and stimulatory (for IL-4) effects of CG were mediated by cAMP, while the effects of steroid hormones on the production of these cytokines were realized through genomic and non-genomic mechanisms (the latter mechanisms were largely mediated by L-type calcium channel regulation). Overall, the studied reproductive hormones could efficiently regulate synthesis of the main Th1 (IFNgamma) and Th2 (IL-4) cytokines by T lymphocytes and seem to play the key role in changing the pregnancy-specific pattern of secreted cytokines.
authors: E M
authors: EM
authors: Kuklina
authors: S V
authors: SV
authors: Shirshov
mesh_terms: D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology / Q000502:physiology; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D016207:Cytokines / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology; D005260:Female; D042341:Gonadal Hormones / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology / Q000502:physiology; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors; D013449:Sulfonamides / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects* / Q000378:metabolism
chemical_list: D006063:Chorionic Gonadotropin; D016207:Cytokines; D042341:Gonadal Hormones; D007546:Isoquinolines; D011980:Receptors, Progesterone; D013449:Sulfonamides; D015847:Interleukin-4; D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol; D007371:Interferon-gamma; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide