Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested mood states in patients with systemic lupus erythematosus (SLE) treated with the prolactin-lowering drug, bromocriptine. Bromocriptine was given to seven patients in an open-label study to test its effects on active SLE. Two independent measures of SLE activity, the SLE Activity Measure (SLAM) and the SLE Disease Activity Index (SLEDAI), were scored and the Symptom Questionnaire (SQ) mood survey was administered at entry and at 6 monthly follow-up visits. The SLAM and SLEDAI scores improved significantly during treatment. Two of the four mood scales in the SQ (Anxiety Scale and Anger-Hostility Scale) showed significant improvement compared to the entry value at least once during treatment. Significant improvement was also observed in the Total Distress Score, which is the sum of the four scales and is a more sensitive measure of distress than the score of an individual scale. Depression, anxiety, somatic complaints, and total distress correlated positively with SLAM and/or SLEDAI scores. The Anxiety Scale and the Total Distress Score improved with treatment and did correlate positively with SLE activity. In contrast, the Anger-Hostility Scale improved with treatment but did not correlate with SLE activity.
Lupus 2000
PMID:Mood states and disease activity in patients with systemic lupus erythematosus treated with bromocriptine. 1103 19

Estrogen can modulate autoimmunity in certain models of systemic lupus erythematosus. Recently, we have shown that it can mediate survival and activation of anti-DNA B cells in a mouse transgenic for the heavy chain of a pathogenic anti-DNA antibody. To identify whether estrogen effects reflect increased prolactin secretion, we characterized B-cell autoreactivity in transgenic mice given both bromocriptine (an inhibitor of prolactin secretion) and estradiol. Treatment of mice with estradiol plus bromocriptine led to reduced titers of anti-DNA antibodies and diminished IgG deposition in kidneys compared with treatment with estradiol alone. However, mice treated with estradiol plus bromocriptine showed an expansion of transgene-expressing B cells and enhanced Bcl-2 expression, similar to those of estradiol-treated mice. We identified anergic high-affinity anti-DNA B cells in mice treated with estradiol plus bromocriptine, and we showed by molecular analysis of anti-DNA hybridomas that their B cells derive from a naive repertoire. Thus, the estradiol-induced breakdown in B-cell tolerance can be abrogated by bromocriptine, which induces anergy in the high-affinity DNA-reactive B cells. These studies demonstrate that some of the effects of estrogen on naive autoreactive B cells require the presence of prolactin and, thus, suggest potential therapeutic interventions in lupus.
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PMID:Bromocriptine restores tolerance in estrogen-treated mice. 1110 90

We investigated the relationships between prolactin (PRL) levels and antibody occurrence in systemic lupus erythematosus (SLE). No significant association between PRL levels and the majority of the autoantibodies studied (anti-U1 RNP, anti-rRNP, anti-Sm, anti-dsDNA, anti-DNP, auto-LCA, anti-EACA) could be confirmed (P > 0.05), anti-Ro/SSA antibodies being an exception. Our results showed significantly increased frequencies of these antibodies in the group of female SLE patients with normal PRL levels (< 20 micrograms/L): anti Ro/SSA in 53% (P < 0.025, chi 2 = 5.80, RR = 4.0) and anti-Ro/SSA + anti-Ro/La in 60% (P < 0.05, chi 2 = 4.05) compared with female SLE patients with hyperprolactinemia.
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PMID:Prolactin levels and autoantibodies in female patients with systemic lupus erythematosus. 1115 10

Prolactin, a lactogenic hormone, is a cytokine and an important link between the immune and endocrine systems. Prolactin stimulated disease in autoimmune NZB/NZW mice. Treatment of the mice with the prolactin-lowering dopamine agonist, bromocriptine, suppressed anti-DNA and prolonged life spans. These findings have been applied to humans with systemic lupus erythematosus (SLE). An open-label study, a double blind study, and a study comparing bromocriptine to hydroxychloroquine provided evidence that bromocriptine therapy reduced flares and suppressed disease activity in SLE.
Lupus 2001
PMID:Treatment of systemic lupus erythematosus with bromocriptine. 1131 52

Inflammation produces reactive oxygen intermediates (ROI) that cause vascular damage and activate T lymphocytes. Conversely, antioxidants not only protect tissue from oxidative damage but also suppress immune reactivity. The objective of this study was to examine immunomodulatory effects of the non-enzymatic antioxidants, N-acetylcysteine (NAC) and cysteamine (CYST), on autoimmune disease, glomerulonephritis, and mortality in the female B/W mouse model of human systemic lupus erythematosus (SLE). The development of murine lupus was assessed during the lifespan of female B/W mice given NAC or CYST. Morbidity and mortality were assessed daily. At 6 week intervals mice were examined for weight change, albuminuria, serum BUN, antibodies to DNA, and IgG immunoglobulin levels. Serum prolactin, estrogen and progesterone were measured at 18 weeks of age. In a parallel study, NAC- and CYST-treated and control B/W mice were examined at 24 weeks of age for interval renal histopathology, lymphocyte adhesion molecule expression, and antibody titers and in vitro cytokine production in response to immunization with DNP-KLH. CYST significantly suppressed development of albuminuria and azotemia at 36 and 42 weeks of age compared to control and NAC-treated mice. NAC significantly suppressed anti-DNA antibody levels at 24 weeks. In contrast CYST significantly increased anti-DNA antibody levels at 18 weeks of age (P < 0.001 CYST vs control and NAC-treated mice). Kidneys of CYST-treated mice also had accelerated inflammatory histologic changes despite their lower incidence of albuminuria and azotemia. Mean (+/- s.e.m.) survival of control mice was 33 +/- 2 weeks compared to 38 +/- 2 weeks in NAC-treated mice (P < 0.05 vs control), and 48 +/- 2 weeks in the CYST-treated group (P < 0.01 vs control mice). The antioxidants, NAC and CYST, significantly improved mortality in the female B/W mouse model of SLE. NAC suppressed autoantibody formation and modestly prolonged survival. CYST, despite its augmentation of anti-DNA levels and renal inflammatory changes, inhibited the development of renal insufficiency and markedly improved survival. These findings suggest that ROIs play a role in the pathogenesis of lupus nephritis and that antioxidants reduce the damage causing renal insufficiency. Antioxidants may be a beneficial adjunctive therapy in the treatment of human SLE.
Lupus 2001
PMID:Antioxidants suppress mortality in the female NZB x NZW F1 mouse model of systemic lupus erythematosus (SLE). 1134 Nov 2

The future promises good news for the treatment of systemic lupus erythematosus, some of which can already be foreseen. Increased knowledge on genes that participate in the predisposition, pathogenesis, pharmacogenetics of, and protection against this disease may permit intervention at this level. Also, better understanding about the role of sex hormones has allowed trials of weak androgens or prolactin inhibitors. New immunomodulators or immunosuppressors may enable more precise treatment at the immunoregulatory level, and greater knowledge on the disturbance of circuits has already provided hints and even allowed trials of anti-interleukin-10 antibodies, an IL-10 decreasing agent, tolerance-induction strategies or intervention at the level of T cell co-stimulation, as well as immune ablation with subsequent stem cell transplantation. Autoantibodies can be removed, controlled by means of anti-idiotypes, which are blocked from reaching their target antigen or uncoupled from the tissues they have reached. All these treatment strategies will gradually become decanted in order to achieve the optimal treatment of SLE, which may tum out to be its cure.
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PMID:The future of treatment for systemic lupus erythematosus. 1134 23

The objective of this study was to determine the diagnostic performance of the percentage of serum prolactin (PRL) precipitated with polyethylene glycol (PEG) for the detection of macroprolactinemia in systemic lupus erythematosus (SLE) patients with hyperprolactinemia. Serum samples from SLE patients were examined. Serum PRL was measured by immunoradiometric assay (IRMA) and samples with hyperprolactinemia (> 20 ng/ml) were submitted to PEG precipitation, gel filtration chromatography and affinity chromatography with protein-G sepharose. A comparative survey was used. Among 259 consecutive serum samples from SLE patients, PRL was > 20.1 ng/ml in 43 samples (16.6%). Gel filtration showed a predominant pattern of macroprolactinemia (> 100 kDa) in 14 (32.6%), a predominant pattern of monomeric PRL (23 kDa) in 27 (62.7%), and a variable pattern in two (4.7%). All sera with a predominant pattern of macroprolactinemia displayed anti-PRL autoantibodies by affinity chromatography for IgG. The best cut-off point for percentage of serum PRL precipitated with PEG for detection of macroprolactinemia was > or = 58.4%. Sensitivity and specificity were 100 and 96.6%, respectively. We can conclude that PEG precipitation is a convenient and simple procedure to screen for the presence of macroprolactinemia in sera from SLE patients. Precipitations > or = 58.4% are indicative of the presence of, and those < 50% the absence of, macroprolactinemia. However, samples with precipitations between 50 and 58.3% require gel filtration chromatography to characterize the predominant molecular form of PRL. Therefore, it is important to take these findings into account in future studies that aim to establish a relationship between PRL and disease activity in SLE.
Lupus 2001
PMID:Detection of macroprolactinemia with the polyethylene glycol precipitation test in systemic lupus erythematosus patients with hyperprolactinemia. 1140 64

Membrane steroid receptors (mSRs) have recently re-emerged as candidates for mediating steroid effects which do not fit the paradigm of nuclear transcription factor mechanisms. We have studied two steroid-binding classes of mSRs, and have noted striking similarities in their characteristics (immunocytochemical appearance, biochemical properties, proteolytic sensitivity, signaling pathways, regulation, and molecular origins). These observations strengthen the conclusion that mSRs can be modified versions of intracellular steroid receptors. The membrane estrogen receptors (mERs) we studied are involved in estrogen-induced release of prolactin. Membrane glucocorticoid receptors (mGRs) in both mouse and human lymphoma cells are necessary for the initiation of glucocorticoid-induced therapeutic apoptosis which is related to the developmental phenomenon of thymic involution. Diseases of autoimmunity such as systemic lupus erythematosus and arthritis are related to estrogen status. Since both of these mSRs have recently been found in both normal and cancerous lymphoid cells, actions of these mSRs may have important consequences for functions and diseases of the immune system. Therefore, the study of these forms of steroid receptors may present novel therapeutic opportunities for the use of steroids and steroid analogs.
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PMID:Membrane estrogen and glucocorticoid receptors--implications for hormonal control of immune function and autoimmunity. 1140 1

Estrogen and prolactin have a reciprocal endocrinologic relationship and both hormones have pleiotropic effects on the immune system. Despite the presence of a number of confounding variables, these hormones modulate autoimmunity; however, mechanisms by which this modulation occurs remain obscure. Estrogen appears to suppress cell-mediated and augment humoral-based immunity. Prolactin appears to stimulate both cell and humoral-based immunity. Both hormones have been shown to modulate IFN gamma secretion. Similar evidence in experimental models, human autoimmune disease, and during pregnancy in autoimmune disease patients suggests disparate effects of estrogen and prolactin on autoimmune responses and disease pathogenesis. In the NZB x NZW F1 mouse model of lupus, prolactin accelerates disease expression, whereas estrogen, devoid of its prolactin stimulating properties, is immunosuppressive and inhibits IL-2 production. Estrogen, because of its endocrinologic and immune effects, may directly or indirectly stimulate or inhibit immune responses. These dichotomous effects have limited its successful pharmacologic manipulation in human autoimmune disease with estrogen compounds, tamoxifen, oral contraceptives, antigonadotropic agents, or ovulation induction regimens. In contrast, reduction of immunostimulatory concentrations of prolactin with bromocriptine has successfully suppressed development or expression of murine and human autoimmune disease. Further investigation into actions and interactions of estrogen and prolactin with autoimmunity will provide a better understanding of the female preponderance of autoimmunity and facilitate a more rational approach to hormonal immunotherapy.
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PMID:Estrogen, prolactin, and autoimmunity: actions and interactions. 1140 18

The objective of this study was to determine the effect of quinagolide (Norprolac) on serum level of cytokines in systemic lupus erythematosus (SLE) patients. In 20 SLE patients treated with a low dose of quinagolide, and in 17 healthy persons who constituted the control group, concentration of serum prolactin (PRL), interleukins (ILs), soluble tumor necrosis factor receptors (sTNF Rs) preceded by calculation of disease activity index (SLEDAI) were tested at entry and then after 3 months in 16 patients and after 6 months in 11 patients who completed the study. Serum PRL level was higher (though insignificantly) in the SLE group than in the controls and decreased significantly after 6 months of therapy. A raised SLEDAI score at entry was significantly reduced during therapy but a weak correlation with PRL level was revealed. A significant increase in IL-6 level in SLE group as compared to controls was observed (respectively 14.57 +/- 13.25 and 5.04 +/- 3.35 microg/ml) as well as a significantly decreased level after 6 months of treatment (4.30 +/- 2.51 pg/ml). There was a significant difference between sTNF RI concentration before and after 3 months of quinagolide treatment (respectively 1140.83 +/- 312.08 and 1454.58 +/- 465.54 pg/ml). After 6 months of treatment a statistically significant correlation between concentration of PRL and level of IL-6 and a negative correlation between PRL and sTNF RI was revealed. Quinagolide treatment may have a role in the management of SLE patients.
Lupus 2001
PMID:Selected serum cytokines in systemic lupus erythematosus treated with quinagolide. 1143 78


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