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)

Induced apoptosis of autoreactive T-lymphocyte precursors in the thymus is crucial for the prevention of autoimmune disorders. IGF-I and prolactin, which are lymphocyte growth factors, may have the potential to suppress apoptosis in thymocytes and thus encourage autoimmunity; conversely, dietary fish oil rich in omega-3 fats appears to upregulate apoptosis in lymphocytes. Since whole-food vegan diets may downregulate systemic IGF-I activity, it is proposed that such a diet, in conjunction with fish oil supplementation and treatment with dopamine agonists capable of suppressing prolactin secretion, may have utility for treating and preventing autoimmune disorders. This prediction is consistent with the extreme rarity of autoimmune disorders among sub-Saharan black Africans as long as they followed their traditional quasi-vegan lifestyles, and with recent ecologic studies correlating risks for IDDM and for multiple sclerosis mortality with animal product and/or saturated fat consumption. Moreover, there is evidence that vegan or quasi-vegan diets are useful in the management of rheumatoid arthritis, multiple sclerosis, and possibly SLE. The dopamine agonist bromocryptine exerts anti-inflammatory effects in rodent models of autoimmunity, and there is preliminary evidence that this drug may be clinically useful in several human autoimmune diseases; better tolerated D2-specific agonists such as cabergoline may prove to be more practical for use in therapy. The moderate clinical utility of supplemental fish oil in rheumatoid arthritis and certain other autoimmune disorders is documented. It is not unlikely that extra-thymic anti-inflammatory effects contribute importantly to the clinical utility of vegan diets, bromocryptine, and fish oil in autoimmunity. The favorable impact of low latitude or high altitude on autoimmune risk may be mediated by superior vitamin D status, which is associated with decreased secretion of parathyroid hormone; there are theoretical grounds for suspecting that parathyroid hormone may inhibit apoptosis in thymocytes. Androgens appear to up-regulate thymocyte apoptosis, may be largely responsible for the relative protection from autoimmunity enjoyed by men, and merit further evaluation for the management of autoimmunity in women. It will probably prove more practical to prevent autoimmune disorders than to reverse them once established; a whole-food vegan diet, coupled with fish oil and vitamin D supplementation, may represent a practical strategy for achieving this prevention, while concurrently lowering risk for many other life-threatening 'Western' diseases.
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PMID:Upregulation of lymphocyte apoptosis as a strategy for preventing and treating autoimmune disorders: a role for whole-food vegan diets, fish oil and dopamine agonists. 1146 Nov 85

Recent accumulated evidence suggests that prolactin (PRL) is an important immunomodulator and plays a part in the pathogenesis of systemic lupus erythematosus (SLE). The current study assessed the frequency of hyperprolactinaemia in patients with SLE and its association with defined clinical manifestations or serological abnormalities. PRL levels were analysed in 60 patients with SLE including a follow-up of 20 patients, 18 patients with rheumatic autoimmune diseases other than SLE (AID) and in 47 normal healthy subjects (NHS) using ELISA. Clinical manifestations and disease activity (ECLAM) were recorded. Autoantibodies (anti-dsDNA, anti-CL) were determined by standard techniques. In all, 28.3% of the patients with SLE had raised serum PRL. Their PRL levels (17.4+/-15.1 ng/ml, P<0.0001) and those of patients with AID (13.1+/-10.3 ng/ml, P<0.001) were significantly higher compared to NHS (6.3+/-3.2 ng/ml). Anti-dsDNA (r(s) = 0.3, P = 0.04) and anti-CL antibody titres (IgG; r(s) = 0.3, P = 0.03) correlated with PRL level. Furthermore, elevated erytthrocyte sedimentation rate (ESR), anaemia, decrease in C3, fatigue, fever and renal involvement were associated with hyperprolactinaemia. These results were confirmed by follow-up examinations. Moderate hyperprolactinaemia is present in a subset of patients with SLE and serum PRL correlates with clinical and serological disease activity.
Lupus 2001
PMID:Enhanced serum prolactin (PRL) in patients with systemic lupus erythematosus: PRL levels are related to the disease activity. 1153 Sep 97

The etiologic enigma of systemic lupus erythematosus (SLE) has so far precluded a fully integrated approach to understanding and managing the disease. As new findings continue to uncover relationships between the endocrine system and the besieged immune system in lupus patients, however, researchers have an opportunity to rethink the direction of their investigative efforts. A successful approach to development of long-awaited new treatments may well include modulation of specific hormones. The peptide hormone prolactin may be associated with SLE disease activity. The dopamine agonist bromocriptine, which inhibits pituitary secretion of prolactin, has been shown in a variety of small animal and human trials to reduce disease activity in SLE. Continued research may show that it can be an attractive alternative or adjacent therapy in cases where hydroxychloroquine is contraindicated.
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PMID:Modulation of hormones in the treatment of lupus. 1168 Jul 80

The aim of the present study was to identify the risk factors for ovarian failure in patients with systemic lupus erythematosus. Seventy-one women aged 17 to 45 years with systemic lupus erythematosus were studied. Patients were interviewed and their medical records reviewed. Demographic characteristics, clinical and serologic profiles, and menstrual and obstetric histories were recorded. Disease activity was measured by the systemic lupus erythematosus disease activity index. Serum FSH, LH, estradiol, progesterone, TSH, prolactin, and antimicrosomal and antithyroglobulin antibodies were measured. Patients who developed ovarian failure were compared to those who did not. Ovarian failure occurred in 11 patients (15.5%) and nine had premature menopause (11.3%). Cyclophosphamide administration and older patient age were found to be associated with ovarian failure. The cumulative cyclophosphamide dose was significantly higher in patients with ovarian failure than in those without this condition (18.9 vs 9.1 g; P = 0.04). The relative risk for ovarian failure in patients with cumulative cyclophosphamide dose higher than 10 g was 3.2. TSH levels were high in 100% of patients with ovarian failure who had received pulse cyclophosphamide. Ovarian failure, and premature menopause in particular, is common in patients with systemic lupus erythematosus, with the most important risk factors being cyclophosphamide dose and age. Thyroid problems may be another risk factor for ovarian failure in patients with lupus.
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PMID:Risk factors for ovarian failure in patients with systemic lupus erythematosus. 1171 9

Prolactin secretion from the anterior pituitary is mediated via dopaminergic pathways. Any process that alters dopamine production or transport in the central nervous system may lead to hyperprolactinemia. Most cases of hyperprolactinemia are due to prolactin secreting pituitary tumors or to medications which alter dopamine production. Prolactinomas cause amenorrhea, galactorrhea and infertility in women and impotence and neurological deficits in men. Dopamine receptor agonists are the mainstay of therapy for hyperprolactinemia as they rapidly lower serum prolactin and cause tumor shrinkage. In this paper we review the regulation of prolactin secretion, the clinical features and causes of hyperprolactinemia, and the use of dopamine agonists.
Lupus 2001
PMID:Pituitary production of prolactin and prolactin-suppressing drugs. 1172 91

Hyperprolactinaemia is associated with systemic lupus erythematosus (SLE) but the mechanism is unknown. Prolactin is expressed not only by pituitary lactotrophic cells but also by T-lymphocytes under the control of an alternative upstream promoter region. T-lymphocytes from SLE patients have been shown to secrete more prolactin than controls, thus implying a possible underlying difference in regulation. This may be due to genetic polymorphism that can be determined by scanning for mutations and using a variety of methods to determine their function. A polymorphism may also be used in disease association studies as it may be in linkage disequilibrium with a disease gene on the same haplotype. Single nucleotide polymorphisms (SNPs) have been found across the prolactin gene region including the extrapituitary and the pituitary promoter regions. These SNPs have been examined for genetic association with SLE and potential effects upon the function of the gene. One SNP in the lymphocyte specific upstream promoter affects prolactin transcription and disease association studies in a cohort of SLE cases demonstrated an increased frequency of the PRL-1149 G allele compared to control subjects. This indicates a possible mechanism for the association of prolactin with SLE. Although prolactin is likely to be one of several predisposing factors in the pathogenesis and progression of SLE, this suggests that manipulation of lymphocyte prolactin production (rather than pituitary production) might be a useful therapeutic approach.
Lupus 2001
PMID:Polymorphisms of the human prolactin gene--implications for production of lymphocyte prolactin and systemic lupus erythematosus. 1172 93

Evidence accumulated over the past 20 y indicates that the anterior pituitary hormone, prolactin (PRL), is a critical, physiologically relevant immunomodulator. Results from early hormone-ablation studies in animals implicated PRL as a factor that contributes to maintenance of immunocompetence. However, the discovery of PRL receptors on T and B lymphocytes and the observation that these cells synthesize and secrete PRL spurred intensive investigation into the actions and underlying mechanisms triggered by the hormone in the immune system. In numerous cell culture systems, PRL was found to act as a co-mitogen, enhancing the efficacy of plant lectins and cytokines in the stimulation of lymphocyte proliferation. In addition, results from more recent studies suggest that PRL may promote survival of certain lymphocyte subsets presumably due to its capacity to augment expression of anti-apoptotic genes. In this review, we focus on the proliferative actions of PRL and its survival promoting properties in immune cells.
Lupus 2001
PMID:Prolactin, a lymphocyte growth and survival factor. 1172 94

The presence of extra-pituitary prolactin and its cognitive receptors in the hematopoietic micro-environment raises the question of whether prolactin plays a role in lympho-hematopoiesis and under what conditions. Current studies suggest that endogenous prolactin does not play a significant role under normal steady-state conditions. Rather, prolactin has been implicated as a 'stress hormone', functioning to restore hematopoietic homeostasis under conditions of dysregulation. The stress response of prolactin as well as its complex relationship with other hormones and factors has resulted in conflicting reports in the literature regarding prolactin's role in lympho-hematopoiesis. A review of this literature is provided as well as discussion of conditions under which lymphohematopoietic activity of prolactin may be evident.
Lupus 2001
PMID:Effects of prolactin on hematopoiesis. 1172 96

Receptors for prolactin (PRL-R) are expressed in normal leukocytes from rat and man. PRL signals through PRL-R associated Janus tyrosine kinase (Jak)-2 and signal transducers and activators of transcription (Stat). In addition, in human leukocytes PRL also activates the p38 MAP kinase pathway. PRL, at physiological concentrations, stimulates the expression of the interferon regulatory factor (IRF)-1 gene in rat spleen and bone marrow cells. In man, genes induced by PRL include several members of the 'suppressors of cytokine signaling' (SOCS) family and inducible nitric oxide synthase (iNOS; in mononuclear cells and in granulocytes) and IRF-1 (in granulocytes). Thus, in normal leukocytes, PRL induces the expression of several genes relevant to innate and acquired immune responses. Sex hormones, such as estrogen and PRL, have been implicated in the pathogenesis of murine and human SLE. Also defective signaling in leukocytes is a feature of the disease. What the origin is of aberrant signaling processes in SLE lymphocytes and how they relate to tolerance breakdown and immunopathology is still unknown. It is not unlikely that PRL is a player at some level. The exact contribution of PRL to immune responses in normal subjects and in SLE patients is not known. Further work should also indicate whether PRL might contribute to the onset or progression of the disease and assess the possible benefits of manipulating PRL concentrations in patients.
Lupus 2001
PMID:Effects of prolactin on signal transduction and gene expression: possible relevance for systemic lupus erythematosus. 1172 98

This manuscript discusses our studies to date concerning the effects of unmodified prolactin (PRL) and phosphorylated PRL on immune function. Most of the discussion refers to effects of changing the ratio of these two forms in maternal PRL on gamma delta T cell development in rat pups in utero, but limited experiments where adult animals have been directly treated are also discussed. The manuscript begins with some general background on gamma delta T cells and the different forms of PRL and then proceeds to a discussion of experimental findings. Results demonstrate that the ratio of unmodified to phosphorylated PRL during rat pregnancy is crucial to normal epidermal gamma delta T cell development in the pup thymus. Elevation of phosphorylated PRL in the dams, by administration of a recombinant molecular mimic of phosphorylated PRL, produces a defect in epidermalgamma delta T cell seeding and subsequent function in the offspring. In contrast, a functional defect is not seen for uterine gamma delta T cells in the offspring, a finding likely reflective of the continued availability of precursors to these cells after the fetal period. Preliminary results from treatment of the NZB/NZW mouse model of lupus with the two forms of PRL suggest opposing effects of unmodified and phosphorylated PRL on one measure of the disease.
Lupus 2001
PMID:Unmodified and phosphorylated prolactin and gamma delta T cell development and function. 1172


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