ИСТИНА

The immunomodulatory role of progesterone (P4) is highly important for successful ovulation, implantation, maintenance of pregnancy and initiation of labor. The functions of progestins are mediated both by nuclear (nPRs) and membrane (mPRs) receptors of adipoQ receptor family. Human peripheral blood mononuclear cells (PBMC) comprise of T and B lymphocytes, monocytes and other types of immune cells, expressing mPRα and mPRβ. Among synthesized progesterone derivatives we found two selective ligands of mPRs which do not interact with nPRs: 19­hydroxypregn­4­ en­20­one and 19­hydroxypregn­3­ene­20­one. The aim of this study was to assess the effects of these selective ligands and P4 on gene expression and the secretion of cytokines (IL­1β, IL­6, IL­10, IL­2, TNFα, TGFβ and IFNγ) in PBMC using qRT­PCR and ELISA. PBMC were isolated from blood of 8 men and 8 women, stimulated with lipopolysaccharide and incubated with different concentration of hormones for 48 hours. P4 and both selective ligands significantly increased gene expression and protein secretion of IL­1β, IL­6 and TNFα and gene expression of TGFβ and IFNγ. IL­10 secretion was reduced significantly after exposure with steroids, whereas mRNA level was unchanged. These compounds also significantly reduced IL­2 mRNA level. Sexual differences in cytokines levels were not detected. The selective ligands of mPRs in some cases acted at lower concentrations on PBMCs than P4 and can successfully replace it without having a side effect on the nPR­positive cells. Thus, P4 and selective analogues of mPRs have both pro­inflammatory and anti-inflammatory effects on PBMC in men and non­pregnant women with mainly pro­inflammatory action. Thus, the concept that progestins have predominantly immunosuppressive effects is oversimplistic. In summary a complex and diverse action of these hormones depending on the type of immune cells, tissue and hormonal context was proposed.