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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the etiology of lupus is imperfectly understood, immune factors, heredity, viral infections, and hormonal status are known to play a role. Studies of the sex ratio of lupus patients indicate that before age 10, twice as many girls as boys are affected, but after 12 years, 9.6 females are affected for each male. The incidence of lupus is almost constant for males of all ages but is much higher for women of fertile age than for other women. The deleterious effect of synthetic estrogens was 1st reported in 1966, and various studies since then have confirmed the results. The etiologic role of pregnancy is debated, but pregnancies can be successfully carried to term in periods of remission. Certain lines of mice spontaneously develop an autoimmune disease resembling disseminated lupus erythematosus. Anti-DNA antibodies appear earlier in the female and death from renal insufficiency occurs earlier than in males. Prepubertal castration does not influence the survival of female mice but significantly reduces that of males. Treatment with estradiol diminishes survival of castrated males and females, while treatment with androgens increases survival time of castrated to control females and of castrated males to that of control males. The timing and dose of treatment modify the response. Progesterone administered alone does not influence survival time of females but somewhat increases that of castrated males. Cyproterone acetate, an antiandrogenous progestin, has no effect in 2-3 week old males. Danazol, a moderately active androgen, has no effect on female mice. Nafoxidine, an antiestrogen, increases survival times. These results support the opinion that estrogens aggravate lupus while androgens have a protective effect. Different hormonal treatments have been prescribed for human lupus. Some beneficial effect for female patients has been observed with danazol, but the drug entails significant hepatic, metabolic, and hypertensive risks and may produce androgenic side effects such as voice modifications and hirsutism. Cyproterone acetate, a derivative of 17-hydroxyprogesterone, is without vascular and metabolic side effects and can halt ovarian function at a dose of 50 mg/day. It behaves as a peripheral antiandrogen and may have androgen agonist activity in some tissues. The mechanism of interaction of sex hormones in lupus may be explained by their influence on cellular and humoral immunity. Estrogens appear to suppress cellular immunity and stimulate humoral immunity, while androgens appear to play a suppressive role at the 2 levels. Contraception for women with lupus must be effective. Combined oral contraceptives and low-dose norsteroid progestins are contraindicated because of their thromboembolic and vascular risks. Low-dose progestins may be used but cause hyperestrogenism in some women. Chlormadinone acetate at a daily dose of 10 mg has no significant vascular effect. IUDs may have reduced efficacy during corticotherapy and pose a risk of infection. Only mechanical vaginal methods ose no threats for lupus patients, but they must be understood and accepted by the patient.
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PMID:[Hormones and lupus]. 391 21

Estrogens appear to play a central role in the immune response and immune-mediated diseases. Recent studies have shown the presence of estrogen receptors on the cells involved in the immune response, namely thymocytes, macrophages and endothelial cells. Particular attention has been focused on the dose-dependent influence of estrogen on the immune response, which appears to be related to the clinical symptoms of autoimmunity (i.e. the effects of pregnancy or oral contraceptive pills). The influence of estrogens on cytokine production by target cells, through interference with their transcriptional activity, has also been the focus of various studies. The effect of estrogens on the expression of the protooncogenes and oncosuppressor genes involved in programmed cell death (apoptosis) might also be relevant to human autoimmunity, in particular the uncontrolled synovial lining cell hyperplasia associated with rheumatoid arthritis and the prolonged T-cell survival in systemic lupus erythematosus. Estrogen-induced immunomodulation is a subject of growing interest and stimulating research.
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PMID:Estrogens, the immune response and autoimmunity. 765 68

Infertile women are treated with various regimens for ovulation induction. The ultimate end-result of these treatments is a significant rise in levels of serum gonadotropins and estradiol--the most potent natural estrogen. Estrogens may affect diverse biologic functions, including immune and inflammatory reactions. A role for estrogens in the development or exacerbation of systemic lupus erythematosus (SLE) has been suggested by many studies. In this report, we present 3 cases of otherwise healthy women who received ovulation induction agents and subsequently developed full-blown SLE. The possible association between this treatment and SLE is discussed.
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PMID:Systemic lupus erythematosus induced by ovulation induction treatment. 757 34

Given the female preponderance of systemic lupus erythematosus (SLE) in humans, the adverse effects of female gender and sex hormones in murine lupus, and numerous reports (retrospective, often anecdotal and uncontrolled) describing a temporal association between estrogen exposure and development or exacerbation of SLE, it is easy to accept that estrogens and SLE simply do not mix. While there are valid concerns regarding the use of exogenous estrogens in women with SLE, there are also potential health benefits to be considered. Several salutary effects of postmenopausal estrogens assume particular importance in SLE where the risks of osteoporosis, exaggerated by menopause (natural or cyclophosphamide-induced) and glucocorticoids, are substantial. Moreover, hormone replacement therapy (HRT) is associated with a 40% reduction in the risk of coronary artery disease, higher levels of high-density lipoprotein-cholesterol, and decreased levels of low-density lipoprotein-cholesterol and plasminogen-activator inhibitor type 1, benefits that should be especially applicable to post-menopausal women with SLE. More recent studies, albeit retrospective and absent the use of validated measures of disease activity, suggest that HRT may be well tolerated. In counseling patients regarding lupus and pregnancy, there are now clinical predictors of pregnancy outcome, and patients in remission tend to have good outcomes. The same principles may be true regarding advice on the use of HRT; patients with inactive or stable/moderate disease and at low risk for thrombosis may benefit without a change in lupus activity. Large prospective double-blind placebo controlled studies inclusive of all ethnic groups such as the Safety of Estrogens in Lupus Erythematosus-National Assessment (SELENA) trial should provide the basis for definitive recommendations.
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PMID:Hormone replacement therapy in postmenopausal women with systemic lupus erythematosus. 945 19

Estrogen receptors are found on vascular endothelial and smooth muscle cells; their expression is influenced by exposure to the hormone. Estrogen receptors influence non-genomic events, which are rapid in onset and genomic events, which are longer acting responses. Estrogens affect vascular tone indirectly by modulating release of endothelium-derived vasoactive factors and directly by modulating intracellular calcium in vascular smooth muscle cells. Estrogens indirectly affect thrombotic events and inflammation by altering platelet aggregation and leukocyte adherence and migration, respectively. Estrogens also influence production of mitogens which, when released at sites of vascular injury, affect vascular remodeling. Although estrogens initiate vascular responses, genomic sex may influence and/or limit expression of estrogen receptors and therefore actions of sex steroid hormones throughout the vasculature.
Lupus 1999
PMID:Gender and vascular reactivity. 1045 23

Estrogens exacerbate the autoimmune disease SLE and progesterone is immunoprotective. Estrogens increase synthesis of progesterone receptors (PR) and it is hypothesized that this physiological balance may be impaired in SLE. To test this, cytosolic PR were measured in hypothalamus, thymus and uterus from 6-week-old female ovariectomized BALB/c and MRL/MP-lpr/lpr mice 48 h after s.c. injection of estradiol benzoate (3.2 microg/0.1 ml; OB) in peanut oil or 0.1 ml peanut oil alone. PR were measured using [(3)H]ORG 2058, which does not bind to corticosteroid-binding globulin (CBG), and bound and free ligand were separated using minicolumns of Sephadex LH20 at 0 degrees C. PR were measured in cytosols from hypothalamus and uterus of oil-treated BALB/c mice, but were undetectable in thymus, whereas receptors were measurable in all three tissues of MRL mice. There was a significantly greater priming effect of OB on PR in uterus of BALB/c mice, but not in hypothalamus, and PR became detectable in thymus cytosols from BALB/c mice. Also, the apparent affinity of the binding reaction between [(3)H]ORG 2058 and PR was significantly higher than those measured in other tissues in hypothalamic cytosols of both strains. These results suggest that there is an impairment of estrogen priming of progesterone receptors in uterus and perhaps thymus of MRL mice.
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PMID:Impaired estrogen priming of progesterone receptors in uterus of MRL/MP-lpr/lpr mice, a model of systemic lupus erythematosus (SLE). 1078 50

RA is an autoimmune rheumatic disorder resulting from the combination of several predisposing factors, including the relation between epitopes of possible triggering agents and histocompatibility epitopes, the status of the stress response system, and the sex hormone status. Estrogens are implicated as enhancers of humoral immunity, and androgens and progesterone are natural immune suppressors. Sex hormone concentrations have been evaluated in RA patients before glucocorticoid therapy and have frequently been found to be altered, especially in premenopausal women and male patients. In particular, low levels of gonadal and adrenal androgens (testosterone and DHT, DHEA and DHEAS) and a reduced androgen:estrogen ratio have been detected in body fluids (i.e., blood, synovial fluid, smears, saliva) of male and female RA patients. These observations support a possible pathogenic role for the decreased levels of the immune-suppressive androgens. Exposure to environmental estrogens (estrogenic xenobiotics), genetic polymorphisms of genes coding for hormone metabolic enzymes or receptors, and gonadal disturbances related to stress system activation (hypothalamic-pituitary-adrenocortical axis) and physiologic hormonal perturbations such as during aging, the menstrual cycle, pregnancy, the postpartum period, and menopause may interfere with the androgen:estrogen ratio. Sex hormones might exert their immune-modulating effects, at least in RA synovitis, because synovial macrophages, monocytes, and lymphocytes possess functional androgen and estrogen receptors and may metabolize gonadal hormones. The molecular basis for sex hormone adjuvant therapy in RA is thus experimentally substantiated. By considering the well-demonstrated immune-suppressive activities exerted by androgens, male hormones and their derivatives seem to be the most promising therapeutic approach. Recent studies have shown positive effects of androgen replacement therapy at least in male RA patients, particularly as adjuvant treatment. Interestingly, the increase in serum androgen metabolism induced by RA treatment with CSA should be regarded as a possible marker of androgen-mediated immune-suppressive activities exerted by CSA, at least in RA and at the level of sensitive target cells and tissues (i.e., synovial macrophages). The absence of altered serum levels of estrogens in RA patients and the reported immune-enhancing properties exerted by female hormones have represented a poor stimulus to test estrogen replacement therapy in RA. The different results obtained with OC use seem to depend on dose-related effects and the different type of response to estrogens in relation to the cytokine balance between Th1 cells (cellular immunity, i.e., RA) and Th2 cells (humoral immunity, i.e., SLE). The androgen replacement obtained directly (i.e., testosterone, DHT, DHEAS) or indirectly (i.e., antiestrogens) may represent a valuable concomitant or adjuvant treatment to be associated with other disease-modifying antirheumatic drugs (i.e., MTX, CSA) in the management of RA.
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PMID:Sex hormone adjuvant therapy in rheumatoid arthritis. 1108 49

Interactions between the immune and nervous systems play an important role in modulating host susceptibility and resistance to inflammatory disease. Neuroendocrine regulation of inflammatory and immune responses and disease occurs at multiple levels: systemically, through the anti-inflammatory action of glucocorticoids released via hypothalamic-pituitary-adrenal axis stimulation; regionally, through production of glucocorticoids within and sympathetic innervation of immune organs such as the thymus; locally, at sites of inflammation. Estrogens also play an important role in immune modulation, and contribute to the approximately 2- to 10-fold higher incidence of autoimmune/inflammatory diseases seen in females of all mammalian species. During inflammation, cytokines from the periphery activate the central nervous system through multiple routes. This results in stimulation of the hypothalamic-pituitary-adrenal axis which, in turn through the immunosuppressive effects of the glucocorticoids, generally inhibits inflammation. Recent studies indicate that physiological levels of glucocorticoids are immunomodulatory rather than solely immunosuppressive, causing a shift in patterns of cytokine production from a TH1- to a TH2-type pattern. Interruptions of this loop at any level and through multiple mechanisms, whether genetic, or through surgical or pharmacological interventions, can render an inflammatory resistant host susceptible to inflammatory disease. Over-activation of this axis, as occurs during stress, can also affect severity of infectious disease through the immunosuppressive effects of the glucocorticoids. These interactions have been clearly demonstrated in many animal models, across species, strains and diseases, and are also relevant to human inflammatory, autoimmune and allergic illnesses, including rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, allergic asthma and atopic skin disease. While many genes and environmental factors contribute to susceptibility and resistance to autoimmune/inflammatory diseases, a full understanding of the molecular effects on immune responses of combinations of neuropeptides, neurohormones and neurotransmitters at all levels has opened up new therapeutic approaches and are essential for the design of future therapies based on such principles.
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PMID:Neuroendocrine regulation of autoimmune/inflammatory disease. 1137 12

Estrogens are believed to play a role in the etiology of both human and murine systemic lupus erythematosus (lupus, SLE), presumably through the agency of their cellular receptor proteins. There is now considerable interest in the molecular mechanism of action of estrogens in immune tissues, particularly with regard to autoimmune disorders, which are generally more prevalent in women. In this laboratory, an attempt is being made to characterize estrogen receptors in murine models of SLE, namely NZB/W and MRL/MP-lpr/lpr mice, and to try to relate this to estrogen receptor function in vivo. It is hypothesized that estradiol (E(2)), through its receptors, mediates the progression of murine SLE and that in autoimmune disease, the estrogen receptor is functionally or structurally changed, or both. Initial studies suggest there are differences in estrogen receptors between BALB/c mice, which do not get autoimmune disease, and two strains that do, MRL/MP-lpr/lpr and NZB/W mice. There is evidence that in at least one model of SLE, the normal regulation of estrogen action by progesterone may be impaired. In several laboratories, attempts are being made to relate estrogen action to immune function and to autoimmune diseases. The study of estrogen action on the immune system may lead to the development of treatments that attenuate the immunostimulant effects of E(2) in autoimmune diseases such as SLE.
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PMID:Lupus: why women? 1138 83

Estrogens are believed to play a role in the etiology of both human and murine systemic lupus erythematosus (lupus; SLE), presumably through the agency of their cellular receptor proteins. There is now considerable interest in the molecular mechanism of action of estrogens in immune tissues, particularly with regard to autoimmune disorders, which are generally more prevalent in women. In this laboratory, an attempt is being made to characterize estrogen receptors in murine models of SLE and to try and relate this to estrogen receptor function in vivo. The initial aim was to compare binding properties of estrogen receptors in brain, reproductive and immune tissues of BALB/c and MRL/MP-lpr/lpr mice. The latter strain spontaneously develops an autoimmune disease resembling human systemic lupus erythematosus (lupus; SLE). It is hypothesized that estradiol, through its receptors, mediates the progression of murine SLE, and that in autoimmune disease, the estrogen receptor is functionally and/or structurally changed. Initial studies suggest that there are differences in estrogen receptors between BALB/c mice, which do not get autoimmune disease, and two strains that do, MRL/MP-lpr/lpr and NZB/W mice. In MRL mice, these differences may be reflected in impaired priming of the progesterone receptor.
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PMID:Estrogen and progesterone receptors in murine models of systemic lupus erythematosus. 1140 99


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