Role of hormone-controlled Th1- and Th2-type cytokines in successful pregnancy

doi:10.1016/S0165-5728(00)00299-X

Journal of Neuroimmunology

Volume 109, Issue 1, 1 September 2000, Pages 30-33

https://doi.org/10.1016/S0165-5728(00)00299-X Get rights and content

Abstract

Development of CD4+ helper T (Th) cells into type 1 (Th1) or type 2 (Th2) effectors, as characterized by their opposite pattern of cytokine production, can be influenced by several factors, including hormones. Progesterone promotes the production of IL-4 and IL-5, whereas relaxin promotes the production of IFN-γ by T cells. Leukemia inhibitory factor (LIF), essential for embryo implantation, is up-regulated by IL-4 and progesterone. Moreover, the production of LIF and/or Th2 cytokines by decidual T cells contributes to the maintenance of pregnancy. Our results suggest that relaxin and progesterone may contribute to the regulation of the immune homeostasis during pregnancy.

Section snippets

Functional properties of human Th1 and Th2 lymphocytes

CD4+ T helper (Th) lymphocytes can be classified into different functional subsets based on their profile of cytokine production. Type 1 Th (Th1) cells produce interferon-γ (IFN-γ), interleukin (IL)-2, and tumor necrosis factor (TNF)-β, and promote the production of opsonizing and complement-fixing antibodies, macrophage activation, antibody-dependent cell cytotoxicity and delayed type hypersensitivity. On the other hand, type-2 Th (Th2) cells produce IL-4, IL-5, IL-6, IL-9, IL-10 and IL-13 and

Hormones can polarize the development of the T cells into Th1 or Th2 cells

The differentiation of Th cells into polarized Th1 or Th2 cells can also be influenced by some hormones. The role of steroid hormones in controlling the patterns of T cell lymphokines produced by activated T cells has also been emphasized. Dihydrotestosterone decreased the quantity of IL-4 and IL-5 produced by activated murine T cells (Vacca et al., 1990; Moynihan et al., 1998), whereas glucocorticoids and 1,25-dihydroxyvitamin D₃ were found to be capable of reducing IL-2 and IFN-γ and

Role of the hormones enhanced during pregnancy on the development of Th1 and Th2 cells

During pregnancy, steroid hormones act systemically in the preparation of the endometrium for implantation, thus establishing ‘the implantation window’. These actions are not only endocrine through specific steroid receptors but also modulate paracrine autocrine effectors such as cytokines.

Progesterone is well known for its immunosuppressive properties (Szekeres-Bartho, 1992). Postcoital administration of a monoclonal antibody against progesterone prevents pregnancy in several species (White et

Hormonal-cytokine network at maternofetal interface

On the basis of these findings, a hormone cytokine network at the maternofetal interface affecting both in blastocyst implantation and maintenance of a successful pregnancy, can be suggested. The observation that fetal development is not impaired, although fetal antigens are recognized as foreign by the mother, is commonly referred to as the immunological paradox of pregnancy. It is well established that pregnancy is associated with modifications in the immune status of the mother, but the

Conclusions

Antithetical Th1/Th2 cytokine profiles appear to characterize pregnancy. We found a linkage between LIF and Th2-type cytokines, and we suggested that a direct cause-and-effect relationship between a local defect of Th2-type cytokine (IL-4 and IL-10) and LIF expression by T cells and pregnancy loss was possible. Strong evidence now indicates that changes in the production of hormones (progesterone and relaxin) play a major role in modulating Th1/Th2 cytokine balance (Piccinni and Romagnani, 1996

References (32)

D. Bani
Relaxin: a pleiotropic hormone
Gen. Pharmacol.
(1997)
C.M. Braun et al.
Corticosteroid modulation of human antigen-specific Th1 and Th2 responses
J. Allergy Clin. Immunol.
(1997)
J.A. Moynihan et al.
Adrenal hormone modulation of type 1 and 2 cytokine production by spleen cells: dexamethasone and dehydroepiandrosterone suppress interleukin-2, interleukin-4 and interferon-gamma production in vitro
Cell Immunol.
(1998)
S. Romagnani
Human Th1 and Th2: doubt no more
Immunol. Today
(1991)
G.A.W. Rook et al.
Hormones, peripherally activated prohormones and regulation of the Th1/Th2 balance
Immunol. Today
(1994)
A. Vacca et al.
Transcriptional regulation of the interleukin 2 gene by glucocorticoid hormones
J. Biol. Chem.
(1990)
J. Visser et al.
Differential regulation of interleukin 10 (IL-10) and IL-12 by glucocorticoids in vitro
Blood
(1998)
Y. Wang et al.
Sex hormones and dexamethasone modulate interleukin-5 gene expression in T lymphocytes
J. Steroid. Biochem. Mol. Biol.
(1993)
T.G. Wegmann et al.
Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a Th2 phenomenon?
Immunol. Today
(1993)
A. Arici et al.
Modulation of leukemia inhibitory factor gene expression and protein biosynthesis in human endometrium
J. Clin. Endocrinol. Metab.
(1995)

G. Chaouat et al.

IL-10 prevents naturally occurring fetal loss in the CBA X DBA/2 mating combination and local defect in IL-10 production in this abortion-prone combination is corrected by in vivo injection of IFN τ

J Immunol.

(1995)

G. Chaouat et al.

Immunoregulatory role of the placenta

J. Immunol. Immunopharmacol.

(1990)

D.S. Charnock-Jones et al.

Leukemia Inhibitory factor mRNA concentration peaks in human endometrium at the time of implantation and the blastocyst contains mRNA for the receptor at this time

J. Reprod. Fertil.

(1994)

J. Culpepper et al.

Regulation of IL-3 expression by glucocorticoids in cloned murine T-lymphocytes

J. Immunol.

(1985)

R.A. Daynes et al.

Locally active steroid hormones may facilitate compartmentalization of immunity by regulating the types of lymphokines produced by helper T cells

Res. Immunol.

(1991)

S.A. Huber et al.

Estradiol prevents and testosterone promotes Fas-dependent apoptosis in CD4+ Th2 cells by altering Bcl2 expression

Lupus

(1999)

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Role of hormone-controlled Th1- and Th2-type cytokines in successful pregnancy

Abstract

Section snippets

Functional properties of human Th1 and Th2 lymphocytes

Hormones can polarize the development of the T cells into Th1 or Th2 cells

Role of the hormones enhanced during pregnancy on the development of Th1 and Th2 cells

Hormonal-cytokine network at maternofetal interface

Conclusions

Gen. Pharmacol.

J. Allergy Clin. Immunol.

Cell Immunol.

Immunol. Today

Immunol. Today

J. Biol. Chem.

Blood

J. Steroid. Biochem. Mol. Biol.

Immunol. Today

Modulation of leukemia inhibitory factor gene expression and protein biosynthesis in human endometrium

J. Clin. Endocrinol. Metab.

IL-10 prevents naturally occurring fetal loss in the CBA X DBA/2 mating combination and local defect in IL-10 production in this abortion-prone combination is corrected by in vivo injection of IFN τ

J Immunol.

Immunoregulatory role of the placenta

J. Immunol. Immunopharmacol.

Leukemia Inhibitory factor mRNA concentration peaks in human endometrium at the time of implantation and the blastocyst contains mRNA for the receptor at this time

J. Reprod. Fertil.

Regulation of IL-3 expression by glucocorticoids in cloned murine T-lymphocytes

J. Immunol.

Locally active steroid hormones may facilitate compartmentalization of immunity by regulating the types of lymphokines produced by helper T cells

Res. Immunol.

Estradiol prevents and testosterone promotes Fas-dependent apoptosis in CD4+ Th2 cells by altering Bcl2 expression

Lupus