Estrogen Decreasesin VitroApoptosis of Peripheral Blood Mononuclear Cells from Women with Normal Menstrual Cycles and Decreases TNF-α Production in SLE but Not in Normal Cultures

doi:10.1006/clin.1996.4300

Clinical Immunology and Immunopathology

Volume 82, Issue 3, March 1997, Pages 258-262

Clinical Immunology ...

https://doi.org/10.1006/clin.1996.4300 Get rights and content

Abstract

Estrogen has been suspected of causing changes in the lupus disease process by an as yet undetermined mechanism.In vitroapoptosis of peripheral blood mononuclear cells (PBMCs) in short-term unstimulated cultures of systemic lupus erythematosus (SLE) cells is accelerated compared to that in cells from normal individuals. To determine whether estrogen might be involved in regulating the rate of apoptosis in lupus, PBMCs or T cells from women with or without normal menstrual cycles were cultured for 16–20 hr with or without 30 ng/ml estradiol. The rate of apoptosis of the cells was measured, and supernatants of these cultures were tested for various cytokines known to affect apoptosis directly or indirectly. Compared to untreated cultures, estrogen significantly reducedin vitroapoptosis of both patient (P< 0.05,n= 12) and normal (P< 0.001,n= 14) PBMCs if the donors had normal menstrual cycles. Estrogen did not decrease apoptosis of noncycling patient (n= 8) nor of normal (n= 11) cells. Apoptosis of T cells cultured alone was not affected by estrogen. Supernatants from patients’ estrogen-treated PBMCs had significantly less TNF-α than untreated cultures (P< 0.05,n= 12). TNF-α levels from normals’ cell cultures were unchanged. Changes in hormone status (hysterectomy or menopause) alter estrogen-sensitive apoptosis, which may be mediated through monocytes. Estrogen-induced decreases in apoptosis combined with decreased TNF-α production in the presence of estrogen may allow survival of autoimmune cells in SLE patients.

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Menopause and Rheumatic Disease
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Citation Excerpt :
Postmenopausal status among the patients was associated with a higher percentage of cells expressing TLRs.40 Another study reported decreased tumor necrosis factor production by estrogen-treated peripheral blood mononuclear cells from patients with SLE.41 Menopause has been studied in relationship to complications of SLE, especially premature atherosclerosis and osteoporosis.
Human cells involved in atherosclerosis have a sex
2017, International Journal of Cardiology
The influence of sex has been largely described in cardiovascular diseases. Atherosclerosis is a complex process that involves many cell types such as vessel cells, immune cells and endothelial progenitor cells; however, many, if not all, studies do not report the sex of the cells. This review focuses on sex differences in human cells involved in the atherosclerotic process, emphasizing the role of sex hormones. Furthermore, we report sex differences and issues related to the processes that determine the fate of the cells such as apoptotic and autophagic mechanisms. The analysis of the data reveals that there are still many gaps in our knowledge regarding sex influences in atherosclerosis, largely for the cell types that have not been well studied, stressing the urgent need for a clear definition of experimental conditions and the inclusion of both sexes in preclinical studies.
Immunomodulatory effects of sex hormones: Requirements for pregnancy and relevance in melanoma
2014, Mayo Clinic Proceedings
Citation Excerpt :
It has been shown that short-term and long-term inflammation leads to the up-regulation of ERα, but not ERβ, thus affecting the effects of estrogens on T cells, because T cells express ERα, while B cells express ERβ.149 It was also reported that estrogen decreases apoptosis, as well as TNF-α production.150 Estradiol-17β and estrone both have a strong affinity for binding ERα,151 which is why ERα is commonly associated with tumor promotion.
Similarities between the pathologic progression of cancer and the physiologic process of placentation (eg, proliferation, invasion, and local/systemic tolerance) have been recognized for many years. Sex hormones such as human chorionic gonadotropin, estrogens, progesterone, and others contribute to induction of immunologic tolerance at the beginning of gestation. Sex hormones have been shown to play contributory roles in the growth of cancers such as breast cancer, prostrate cancer, endometrial cancer, and ovarian cancer, but their involvement as putative mediators of the immunologic escape of cancer is still being elucidated. Herein, we compare the emerging mechanism by which sex hormones modulate systemic immunity in pregnancy and their potentially similar role in cancer. To do this, we conducted a PubMed search using combinations of the following keywords: “immune regulation,” “sex hormones,” “pregnancy,” “melanoma,” and “cancer.” We did not limit our search to specific publication dates. Mimicking the maternal immune response to pregnancy, especially in late gestation, might aid in design of better therapies to reconstitute endogenous antitumor immunity and improve survival.
Gender and Age in Lupus
2011, Systemic Lupus Erythematosus
The relationship between age and the morbidity and mortality of systemic lupus erythematosus (SLE) is important and the incidence of disease varies in males and females depending on age. Gender and more specifically sex steroids play an important role in the maturation of organ systems that affect animals throughout life and are therefore important to the health of most vertebrates. The effects of sex steroids on the immune system are profound and long-lasting because they control the growth and maturation of various cell systems and may also influence susceptibility to disease through modulation of immune cell populations, alteration of cytokine levels, control of cell populations through processes such as apoptosis, and change of very basic molecular mechanisms. Lupus is one disease that is highly affected by hormones. Thus, sex steroids are potent modulators of immunity in all animal systems. They are very important in patients with SLE and may help explain the fluctuant activity in lupus disease. Their role in the maturation of the immune system and their effect on the development of organs such as the brain could explain some of the abnormalities found in these systems.
Gender Differences in Autoimmune Diseases. Immune Mechanisms and Clinical Applications
2010, Principles of Gender-Specific Medicine
This chapter updates and adds new information to complement and extend previous reviews on gender differences in autoimmunity. It starts with general remarks on what is new in sex hormones and autoimmunity. It then discusses genes and sex differences with respect to autoimmune diseases, immune mediators, and signals that are under the influence of sex hormones, and updates the information on estrogen receptors (ER), both ERα and ERβ. The chapter discusses immune modulation following activation and/or blocking of estrogen receptors and the subsequent expression of the autoimmune state. In this chapter, recent work was selected that dealt with hormones and gender differences in autoimmunity. The interplay between sex hormones and the cellular–humoral–cytokine factors that could influence the expression of autoimmune diseases is discussed. Specific autoimmune diseases with female predominance are discussed with emphasis on systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren syndrome (SS), and neurologic diseases, particularly those with established animal models. Current and future applications of the basic information in the field of hormones and gender are outlined with emphasis on possible future therapeutic applications in autoimmune diseases with female predominance.
Sex Hormones and Immune Function
2010, Principles of Gender-Specific Medicine
The entire area of steroid biochemistry and metabolism remains one of the most controversial in both endocrinology and immunology. The convergence of these two disciplines can be difficult because there is little known about the effects that phenomena in one specialized area have on the other. In this chapter the metabolic changes found in a variety of autoimmune diseases are described. The full importance of these changes, where they occur, and their effects on the immune system are not fully known. Various changes of cytokines in response to shifting levels of sex steroids are known to occur, but at the level of a particular organ like the ovary or the liver such responses may only be apparent over long periods of time. Such changes at the “local” level have effects on the host, but the complexity of these effects and careful study of the initial stimulus is the material of future research and presently only speculation. Sex steroids are important to the development of various organs, and a major one is the brain. Recent attention is directed to cerebral development, cerebral dominance, and the incidence of autoimmune disease. Some studies say that patients with autoimmune disease are predominantly left-handed, indicating dominance of the right cerebral hemisphere. This variation is reported in patients with SLE and other diseases of the immune system. Neuronal migration is under the influence of steroids like testosterone, and new data suggest that SLE mice have aberrant neuronal migration patterns consistent with those observed in humans with learning disabilities like dyslexia.

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^☆: R. G. Lahita, Ed.

¹: To whom correspondence should be addressed.

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Clinical Immunology and Immunopathology

Abstract

References (25)

Nucleosomes and DNA bind to specific cell-surface molecules on murine cells and induce cytokine production

Clin. Immunol. Immunopathol.

The spontaneous apoptotic cell death of normal human lymphocytesin vitro:in vitro

Clin. Immunol. Immunopathol.

Presence of a variant form of the estrogen receptor in peripheral blood mononuclear cells from normal individuals and lupus patients

J. Reprod. Immunol.

Sex and age in systemic lupus erythematosus

Systemic Lupus Erythematosus

The mother in SLE

Autoantibodies typical of non-organ-specific autoimmune diseases in HIV-seropositive patients

AIDS

Accelerated in vitro apoptosis of lymphocytes from patients with systemic lupus erythematosus

J. Immunol.

Lpr and gld: Single gene models of systemic autoimmunity and lymphoproliferative disease

Annu. Rev. Immunol.

Special article: The 1982 revised criteria for the classification of systemic lupus erythematosus

Arthritis Rheum.

A reliability study of SLEDAI a disease activity index for systemic lupus erythematosus

J. Rheum.

Mechanisms of action of steroid hormones

Estrogen and progesterone receptors in vessel walls: Biochemical and immunochemical assays

Acta Obstet. Gynecol. Scand.

Cited by (89)

Menopause and Rheumatic Disease

Human cells involved in atherosclerosis have a sex

Immunomodulatory effects of sex hormones: Requirements for pregnancy and relevance in melanoma

Gender and Age in Lupus

Gender Differences in Autoimmune Diseases. Immune Mechanisms and Clinical Applications

Sex Hormones and Immune Function

Regular ArticleEstrogen Decreasesin VitroApoptosis of Peripheral Blood Mononuclear Cells from Women with Normal Menstrual Cycles and Decreases TNF-α Production in SLE but Not in Normal Cultures☆

Abstract

Clin. Immunol. Immunopathol.

Clin. Immunol. Immunopathol.

J. Reprod. Immunol.

Sex and age in systemic lupus erythematosus

Systemic Lupus Erythematosus

The mother in SLE

Autoantibodies typical of non-organ-specific autoimmune diseases in HIV-seropositive patients

AIDS

Accelerated in vitro apoptosis of lymphocytes from patients with systemic lupus erythematosus

J. Immunol.

Lpr and gld: Single gene models of systemic autoimmunity and lymphoproliferative disease

Annu. Rev. Immunol.

Special article: The 1982 revised criteria for the classification of systemic lupus erythematosus

Arthritis Rheum.

A reliability study of SLEDAI a disease activity index for systemic lupus erythematosus

J. Rheum.

Mechanisms of action of steroid hormones

Estrogen and progesterone receptors in vessel walls: Biochemical and immunochemical assays

Acta Obstet. Gynecol. Scand.

Regular Article
Estrogen Decreasesin VitroApoptosis of Peripheral Blood Mononuclear Cells from Women with Normal Menstrual Cycles and Decreases TNF-α Production in SLE but Not in Normal Cultures☆