Review Paper: Effects of Estrogen and Progesterone on Different Immune Cells Related to Multiple Sclerosis (original) (raw)
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Effects of Estrogen and Progesterone on Different Immune Cells Related to Multiple Sclerosis
Caspian Journal of Neurological Sciences
Multiple Sclerosis (MS) is a chronic autoimmune disease of young adults with an unknown etiology, but cellular immune responses and inflammation has a pivotal role in this regard. The higher incidence of MS among women indicates the possible involvement of female sex hormones on the disease course. Progesterone and estrogen are the most important sexual hormones in women. They exert different immunomodulatory effects through both nuclear and membrane associated receptors present in different immune cells. The immunological effects include shifting the immune response towards Th2, stimulating Treg production, inhibiting pro-inflammatory cytokine production, prohibiting cell migration into Central Nervous System (CNS), suppressing proinflammatory immune cells, stabilizing the neuronal environment, and promoting neuronal survival, all of which might ameliorate the condition in women suffering from MS. Some clinical trials have reported a correlation between the use of Oral Contraceptives (OCs), which contain estrogen and progesterone, and MS among women. Some of these studies show a positive effect of OC usage on the onset and severity of the disease while others have found no significant impact. In this review, we collected articles published between 1995 and 2017 from PubMed Central and Google Scholar for evaluating effects of estrogen and progesterone on different immune cells related to MS.
Journal of Reproductive Immunology, 2018
To prospectively study systemic in vivo immunological effects of sex hormones, using different phases of oral combined hormonal contraceptives (CHC), and the natural menstrual cycles in both healthy women and in women with multiple sclerosis (MS), blood samples from sixty female MS patients and healthy controls with and without CHC were drawn in high and low estrogenic/progestogenic phases. Expression of Th-associated genes in blood cells was determined by qPCR and a panel of cytokines and chemokines was measured in plasma. High hormone level phases were associated with increases in Th1 (TBX21) and Th2 (GATA3) associated markers, as well as the B cell-associated chemokine CXCL13, while the inhibitory regulator CTLA-4 was decreased. These changes were not observed in MS patients, of whom most were treated with immunomodulatory drugs. Our data indicate immune activating properties in vivo of high steroid sex hormone levels during both CHC and normal menstrual cyclicity.
Sex Hormones as Key Modulators of the Immune Response in Multiple Sclerosis: A Review
Biomedicines
Background: A variety of autoimmune diseases, including MS, amplify sex-based physiological differences in immunological responsiveness. Female MS patients experience pathophysiological changes during reproductive phases (pregnancy and menopause). Sex hormones can act on immune cells, potentially enabling them to modify MS risk, activity, and progression, and to play a role in treatment. Methods: Scientific papers (published between 1998 and 2021) were selected through PubMed, Google Scholar, and Web of Science literature repositories. The search was limited to publications analyzing the hormonal profile of male and female MS patients during different life phases, in particular focusing on sex hormone treatment. Results: Both men and women with MS have lower testosterone levels compared to healthy controls. The levels of estrogens and progesterone increase during pregnancy and then rapidly decrease after delivery, possibly mediating an immune-stabilizing process. The literature exam...
Effects of sex hormones on costimulatory molecule expression in multiple sclerosis
Journal of Neuroimmunology, 2005
Sex hormones play a central role as modulators of immune responses and autoimmune diseases. We hypothesized that suppression of MS disease during pregnancy may be mediated by sex steroid hormones via regulation of costimulatory molecules such as CD40L or CD80/CD86 (B7-1/B7-2). We tested two sex hormones that are implicated in immune suppression during pregnancy: estriol and progesterone. We also examined whether this regulation is gender-specific or disease-related. PBMC from untreated relapsing remitting multiple sclerosis (RR MS) patients and controls were examined for expression of T cell and monocyte costimulatory molecules following mitogen stimulation in the presence or absence of sex hormones. In the absence of hormones, we confirmed that mitogen stimulation induced significantly more CD40L on the surface of CD4(+)T cells in MS patients compared to controls, and we extend these findings by showing there were no gender differences in induction of CD40L. Although supra-physiologic doses of hormones mildly suppressed CD40L expression on activated T cells, in vitro exposure to typical pregnancy-related physiologic doses of estriol or progesterone showed very little or no suppression of CD40L. On monocytes, neither estriol nor progesterone significantly altered the expression of CD80/CD86. These results suggest that physiologic doses of estriol or progesterone cannot alter CD40L on T cells or CD80/CD86 on monocytes sufficiently to explain the improvement observed in MS during pregnancy. Thus, although amelioration of MS and other autoimmune diseases during pregnancy is thought to be due to increased sex hormones, the present results do not support a role for suppression of costimulation via estriol or progesterone.
Hormonal influences in multiple sclerosis: New therapeutic benefits for steroids
Maturitas, 2011
Multiple sclerosis (MS) is one of the most common neurological disorders. It affects mainly women. This autoimmune disease of the central nervous system (CNS) is characterized by intermittent or chronic damage to the myelin sheaths (demyelination), focal inflammation and axonal degeneration. During the early relapsing/remitting stages of MS, myelin can regenerate, but as the disease progresses the remyelination of axons becomes insufficient, leading to impaired axon conduction, neurodegeneration and the worsening of symptoms. The present pharmacological treatment of MS is limited to the administration of immunomodulatory and anti-inflammatory drugs, which are only palliative and do not significantly slow progress of the disease. What are needed are agents that target different cell types in the CNS to protect axonal networks and stimulate the endogenous capacity of myelin repair. Estrogens and progestins may be the basis for such a new therapeutic approach. Although clinical observations provide only indirect or insufficient evidence for an influence of sex steroids on the progress of MS, experimental studies have shown that estrogens and progestins exert multiple beneficial effects in experimental autoimmune encephalomyelitis (EAE), a widely used MS disease model. Moreover, both types of hormones have been shown to promote the viability of neurons and the formation of myelin. These promising experimental results should encourage the launch of prospective clinical studies to clarify the influence of hormones on the course of MS and the effect of hormone treatments, in particular those presently used in contraception and hormone replacement therapy (HRT).
Immune Modulation in Multiple Sclerosis Patients Treated with the Pregnancy Hormone Estriol
The Journal of Immunology, 2003
The protective effect of pregnancy on putative Th1-mediated autoimmune diseases, such as multiple sclerosis and rheumatoid arthritis, is associated with a Th1 to Th2 immune shift during pregnancy. The hormone estriol increases during pregnancy and has been shown to ameliorate experimental autoimmune encephalomyelitis and collagen-induced arthritis. In addition, estrogens induce cytokine changes consistent with a Th1 to Th2 shift when administered in vitro to human immune cells and in vivo to mice. In a pilot trial, oral estriol treatment of relapsing remitting multiple sclerosis patients caused significant decreases in enhancing lesions on brain magnetic resonance imaging. Here, the immunomodulatory effects of oral estriol therapy were assessed. PBMCs collected longitudinally during the trial were stimulated with mitogens, recall Ags, and glatiramer acetate. Cytokine profiles of stimulated PBMCs were determined by intracellular cytokine staining (IL-5, IL-10, IL-12 p40, TNF-α, and I...
Gender and sex hormones in multiple sclerosis pathology and therapy
Frontiers in Bioscience, 2009
Several lines of evidence indicate that gender affects the susceptibility and course of multiple sclerosis (MS) with a higher disease prevalence and overall better prognosis in women than men. This sex dimorphism may be explained by sex chromosome effects and effects of sex steroid hormones on the immune system, blood brain barrier or parenchymal central nervous system (CNS) cells. The well known improvement in disease during late pregnancy has also been linked to hormonal changes and has stimulated recent clinical studies to determine the efficacy of and tolerance to sex steroid therapeutic approaches. Both clinical and experimental studies indicate that sex steroid supplementation may be beneficial for MS. This could be related to anti-inflammatory actions on the immune system or CNS and to direct neuroprotective properties. Here, clinical and experimental data are reviewed with respect to the effects of sex hormones or gender in the pathology or therapy of MS or its rodent disease models. The different cellular targets as well as some molecular mechanisms likely involved are discussed.
Symptoms of multiple sclerosis in women in relation to sex steroid exposure
Maturitas, 2006
Objective: To investigate if women with multiple sclerosis (MS) experience changes in MS symptoms related to pregnancy, the postpartum period, menopause or use of oral contraception (OC) or postmenopausal hormone therapy (HT). Methods: Women with diagnosed MS were recruited from registers of all MS patients known in two counties of Sweden, respectively. Ninety-four women were recruited in Linköping and 52 in Sundsvall. The women answered a questionnaire with categorized alternatives regarding their MS symptoms related to menstruation, pregnancy, delivery, menopause and use of OC or HT. Results: Forty percent of the women reported worsening of MS symptoms related to menopause, whereas 56% reported no change of symptoms and 5% reported decreased symptoms. More than a fourth of the women reported decreased symptoms during pregnancy, 64% reported unchanged symptoms and 10% reported increased symptoms. Every third woman reported increased symptoms after delivery, 59% reported no change and 5% reported decreased symptoms. Few women reported changes in MS symptoms in relation to use of HT or OC. Conclusion: The presented data indicate a relationship between high-oestrogen states and ameliorated symptoms whereas low-oestrogen states seem to relate to a worsening of the disease. A majority of women, however, reported no changes in MS symptoms in relation to the different oestrogen states.