Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogen is known to influence immune responses in healthy subjects in a dichotomous fashion. Thus, in number of previous studies we and others have demonstrated that B cell activities are augmented after exposure to estrogen whereas T cell reactivity is suppressed. Furthermore, it has been shown that this hormone has significant impact on the course of certain human and experimental autoimmune diseases. In this study we report that treatment with physiological doses of estradiol exerts dichotomous effects on different manifestations of the lupus disease in MRL/l mice. On one hand immune complex-mediated glomerulonephritis was significantly accelerated. This outcome was due to polyclonal B cell activation with increased production of antibodies to double-stranded DNA and formation of circulating immune complexes. In contrast, T cell-mediated lesions such as focal sialadenitis, renal vasculitis, and periarticular inflammation were all significantly ameliorated in MRL/l mice exposed to estrogen. Thus, we were able to demonstrate that, within one subject and even within one organ, administration of estrogen leads to differential outcome of SLE morbidity. We propose that the differential effect of estrogen on the manifestations of the autoimmune disease of MRL/l mice is due to its dichotomous effects on B and T cell-mediated immune responses.
 ...
PMID:Estrogen accelerates immune complex glomerulonephritis but ameliorates T cell-mediated vasculitis and sialadenitis in autoimmune MRL lpr/lpr mice. 139 37

US and British studies have shown significantly higher incidence of strokes due to thromboembolism, subarachnoid hemorrhage, and cerebral venous thrombosis in users of oral contraceptives, particularly high estrogen formulations. Estrogen increases plasma levels of fibrinogen and the clotting factors VII, VIII, IX, X, and XII; enhances platelet aggregation; and suppresses antithrombin III and the fibrinolytic system. Estrogen may also cause immune-mediated vasculitis. The risk of strokes increases for women over 35 and smokers. Estrogen-induced chorea, including chorea of pregnancy, may be due to direct dopaminergic action of estrogens or to an accumulation of dopamine in the brain caused by competitive binding to the dopamine-degrading enzyme catechol-o-methyltransferase. Epileptics taking anticonvulsants and oral contraceptives have 25 times the risk of pill failure as normally expected, due to metabolism of anticonvulsants, such as phenytoin, phenobarbital, primidone, carbamazepine, and ethosuximide, by the hepatic microsomal enzyme system, resulting in a dramatic decrease of circulating ethinyl estradiol. Available options are to increase the estrogen dose to as much as 100 mg, to substitute valproic acid for other anticonvulsants, or to augment ethinyl estradiol levels by oral administration of ascorbic acid, which increases the bioavailability of the steroid. During pregnancy, on the other hand, serum levels of anticonvulsants decrease by 30-40%.
 ...
PMID:Sex hormones in stroke, chorea, and anticonvulsant therapy. 305 49

Estrogen replacement therapy has been demonstrated to shift the lipoprotein profile toward a less atherogenic one with concomitant increases in HDL and reductions in LDL cholesterol and serum triglycerides. Estrogen, however, has also been implicated in playing a significant role in autoimmune disease and may be involved with disease incidence and progression. The MRL/lpr mouse strain represents an autoimmune disease model with features resembling systemic lupus erythematosus including high-titer autoantibodies, glomerulonephritis, and vasculitis. In the present study, the effects of estrogen treatment on serum lipoprotein profiles were investigated by fast protein liquid chromatography in female MRL/lpr mice, in the MRL/++ strain with a milder form of disease, and in control Balb/c mice. Treatment of MRL/lpr mice for periods of 1 week or longer with pharmacologic doses of estrogen resulted in a significant increase in the amount of cholesterol carried on LDL particles. The up to eightfold increase in LDL cholesterol was less significant in the MRL/++ or Balb/c mice. Maximal increases were observed at 1 to 2 mg/kg of estrogen agonists, and the effect on LDL cholesterol increases was inhibited by tamoxifen. The HDL-to-LDL shift in cholesterol observed in estrogen-treated autoimmune mice correlated with an increase in apolipoprotein E, primarily on larger HDL particles. In addition to the increase in LDL cholesterol, hormonal treatment also resulted in a shift in triglycerides from the VLDL to the LDL fraction in both normal and autoimmune mice. These results suggest that pharmacologic doses of estrogen may contribute to cardiovascular disease progression by shifting the relative distribution of cholesterol from HDL to LDL in this murine model of lupus.
 ...
PMID:Estrogen-induced alterations in lipoprotein metabolism in autoimmune MRL/lpr mice. 758 27

Systemic lupus erythematosus (SLE) predominantly affects women (9:1 compared to men) of childbearing age and often decreases its intensity in postmenopausal women, suggesting that sex hormones play a role in its pathogenesis. Comparison of steady-state levels of calcineurin mRNA using RNase protection assays revealed increased calcineurin expression in response to estradiol in cultured T cells from nine female lupus patients. Calcineurin mRNA levels did not increase significantly in T cells from eight age-matched normal control female volunteers. Estrogen-dependent calcineurin mRNA increased in a dose-dependent fashion, while progesterone and dexamethasone did not increase calcineurin mRNA in patient cells. Lupus T cell calcineurin mRNA increased in response to estradiol at 6 h but not at 3 h. Calcineurin phosphatase activity increased in lupus T cell extracts after incubation of cells with estradiol, while phosphatase activity in normal T cells was unaffected by estrogen. Calcineurin expression in T cells from patients with vasculitis and rheumatoid arthritis taking medications similar to those taken by the lupus patients was unaffected by estradiol. This study provides the first evidence for a molecular marker of estrogen action in lupus patients and suggests that estrogen-dependent changes in lupus T cell calcineurin could alter proinflammatory cytokine gene regulation and T-B cell interactions.
 ...
PMID:Gender differences in autoimmune diseases: estrogen increases calcineurin expression in systemic lupus erythematosus. 983 88

The cause or mechanism of the female predisposition in systemic lupus erythematosus and progressive systemic sclerosis is largely unknown. Accumulating evidence shows that dysfunction or activation of endothelial cells plays an important role in these conditions. In this study, we investigated the influence of various steroid hormones on the IL-1beta (50 U/mL)/TNF-alpha (50 U/mL) stimulated human dermal microvascular endothelial cell line (HMEC-1) and human umbilical vein endothelial cells (HUVEC). Dexamethasone showed significant inhibition of cytokine-induced ICAM-1 expression in HMEC-1, and E-selectin, VCAM-1 and ICAM-1 expressions in HUVEC. Androgens, especially dihydrotestosterone had a small, but statistically significant suppressive effect in HMEC-1 only. Estrogen exhibited no regulatory function in either cell line. No obvious expression of estrogen and androgen receptors could be demonstrated in either cell by immunostaining. Our study provided some pharmacological evidence that the superior anti-inflammatory effect of glucocorticoids on vasculitis was partly due to their inhibition of the CAM expression in endothelial cells. More studies are needed to determine if androgens could have a protective effect in vasculitis or vasculopathy associated with connective tissue diseases.
 ...
PMID:Effects of dexamethasone and sex hormones on cytokine-induced cellular adhesion molecule expression in human endothelial cells. 1237 Jan 31