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

Cyclosporin A is widely used in organ transplantation, preventing the rejection of multiple types of organ allografts. It is also being increasingly used as an immunosuppressive agent to treat various autoimmune diseases in patients refractory to more commonly used immunosuppressive therapy. Several trials are currently evaluating the utility of this drug associated with corticosteroids in the treatment of systemic lupus erythematosus. This case, describing a lethal septicaemia caused by Listeria monocytogenes in a patient receiving this treatment, seems to indicate that the use of these "cocktails" of immunosuppressive drugs should be particularly cautious to prevent fatal infectious complications.
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PMID:Fatal septicaemia due to Listeria monocytogenes in a patient with systemic lupus erythematosus receiving cyclosporin and high prednisone doses. 160 11

MRL-lpr/lpr mice develop T cell lymphadenopathy, polyclonal activation of B lymphocytes, autoantibodies and lupus nephritis. B and T cell populations, the dysfunctions of which play a role in the pathophysiology of the mouse disease, represent potential targets for lupus treatment. MRL-lpr/lpr mice are treated from the age of 19 weeks, i.e. after the onset of renal disease and lymphoproliferation, with Cyclosporin A which acts at the T cell level, or with DIAM4 which can down modulate polyclonal activation of B lymphocytes. DIAM4 induces the disappearance of the lymphoproliferation, the increase in C3 levels and the decrease in anti-DNA antibody, immunoglobulin and urea levels, and proteinuria. Cyclosporin A reduces lymph node hyperplasia, but has no effect on other parameters of the disease.
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PMID:Treatment of end stage MRL-1pr/lpr mouse lupus disease by a cyclophosphazene derived drug and by cyclosporin A. 196 44

Cells of the immune system synthesize prolactin and express mRNA and receptors for that hormone. Interleukin 1, interleukin 6, gamma interferon, tumor necrosis factor, platelet activator factor, and substance P participate in the release of prolactin. This hormone is involved in the pathogenesis of adjuvant arthritis and restores immunocompetence in experimental models. In vitro studies suggest that lymphocytes are an important target tissue for circulating prolactin. Prolactin antibodies inhibit lymphocyte proliferation. Prolactin is comitogenic with concanavalin A and induces interleukin 2 receptors on the surface of lymphocytes. Prolactin stimulates ornithine decarboxylase and activates protein kinase C, which are pivotal enzymes in the differentiation, proliferation, and function of lymphocytes. Cyclosporine A interferes with prolactin binding to its receptors on lymphocytes. Hyperprolactinemia has been found in patients with systemic lupus erythematosus. Fibromyalgia, rheumatoid arthritis, and low back pain patients present a hyperprolactinemic response to thyrotropin-releasing hormone. Experimental autoimmune uveitis, as well as patients with uveitis whether or not associated with spondyloarthropathies, and patients with psoriatic arthritis may respond to bromocriptine treatment. Suppression of circulating prolactin by bromocriptine appears to improve the immunosuppressive effect of cyclosporine A with significantly less toxicity. Prolactin may also be a new marker of rejection in heart-transplant patients. This body of evidence may have an impact in the study of rheumatic disorders, especially connective tissue diseases. A role for prolactin in autoimmune diseases remains to be demonstrated.
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PMID:Prolactin, immunoregulation, and autoimmune diseases. 206 74

Autoimmune diseases arise when autoimmunity or the loss of self tolerance results in tissue damages. Many mechanisms have been proposed for the origin of autoimmunity, including immunologic, viral, hormonal and genetic factors. All known parts of the immunological network are involved in causing immunopathologic symptoms. Therefore, more or less specific immunosuppressants are widely used in the treatment of autoimmune disorders which range from organ-specific, i.e. Hashimoto's thyroiditis, to non-organ-specific or systemic diseases, i.e. systemic lupus erythematosus. Unspecifically acting cytostatics do not only suppress autoimmune reactions but also create severe side-effects due to the impairment of immune responses against foreign antigens, leading, for example, to an increased risk of infections. Moreover, the genotoxic activity of cytostatics might induce malignancies. Corticosteroids are clinically well known and very active agents for the management of acute symptoms but different side-effects limit their use in the treatment of chronic diseases. Cyclosporin A has been an important step forward to a more specific prevention of organ transplant rejections and to the therapy of some autoimmune disorders. Modern approaches to immunosuppression include monoclonal antibodies directed against a variety of different determinants on immunocompetent cells. Ciamexone and Leflunomide which are in early clinical and preclinical development, respectively, might be interesting new drugs. Future immunopharmacologic drug research and development should lead to more specific, low molecular weight, orally active and chemically defined immunosuppressive compounds with good tolerability under long-term treatment of autoimmune diseases.
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PMID:Drugs in autoimmune diseases. 219 87

We report the history of 2 teenagers suffering from systemic lupus erythematosus for more than 5 years. Both of them were treated with total plasma exchange (TPE) and Ciclosporin A. They responded well to this therapy and achieved remissions. Especially the 2nd patient showed a dramatic clinical improvement after a relapse caused by sun exposure. Both treatment modalities are discussed and the following conclusions are drawn: TPE is an important therapeutic element in treating patients with SLE, whereas Ciclosporin A is not recommended for therapy of first choice. Further prospective and controlled studies have to show, if there is a benefit of this therapy, especially in childhood.
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PMID:[Status of plasmapheresis and cyclosporin A in the treatment of systemic lupus erythematosus]. 239 9

Ciclosporin A (CYA) is a newly developed immunosuppressant and has a sparing effect on suppressor cell regulatory mechanism. However, accumulation of experimental animal studies has not been enough for the administration of CYA to human autoimmune diseases such as lupus nephritis. In this study, the histopathological aspects of the kidney in (NZB x NZW)F1 mice after administration of CYA were analysed. A dose of 25 mg/kg/day of CYA was injected intraperitoneally so that serum level of CYA was controlled from 250 to 300 ng/ml with this dosage. Typical histopathological changes of lupus nephritis including wire-loop lesions were observed in the kidney of the non-treated control group. In contrast, only few lesions were demonstrated in the CYA-treated group. These results suggest that CYA prevented the renal deterioration in lupus mice.
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PMID:The effects of ciclosporin on the renal histopathological aspects in (NZB x NZW)F1 mice. 260 Nov 14

New aspects of pathogenesis, diagnosis and treatment of renal involvement in classic generalized immune diseases are reported. In Good-pasture's syndrome survival is now possible with high-dose corticosteroids, cyclophosphamide pulse therapy and plasmapheresis. Renal transplantation can be performed with no recurrence of disease once the production of autoantibodies against basal membranes has stopped. Patients with Wegener's disease die if adequate treatment is not provided. Long-term cyclophosphamide therapy can induce complete remission. A solid-phase radioimmunoassay for detection of circulating autoantibodies to neutrophilic cytoplasmic antigens is helpful in the diagnosis and monitoring of therapy. In systemic lupus erythematosus, renal biopsy is only mandatory to solve the question as to whether high-dose steroid treatment should be prescribed: only in the case of diffuse proliferative glomerulonephritis will corticosteroids be beneficial. Intermittent pulse therapy with cyclophosphamide seems to slow down the progression of renal failure, whereas a positive effect of plasmapheresis has not been proven. Cyclosporin A reduces the dosage of corticosteroids needed.
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PMID:[Kidney involvement in autoimmune diseases]. 268 78

The renal glomeruli are vulnerable to injury by a number of drugs and other toxic agents. These agents may lead to damage by one of two basic mechanisms: direct, dose-related toxic injury; indirect, immunologically mediated injury, largely dose-independent. Proteinuria is the simplest and most important functional indicator of glomerular injury. It occurs almost immediately in direct toxic injury, but there is a latent period of weeks to months with immunologically mediated processes. Of the two mechanisms, the second is by far the more common in clinical settings. The best studied experimental agent causing direct toxic injury is the aminonucleoside of puromycin. Clinically, perhaps the most important agent is Cyclosporine A. Although this agent is usually thought of primarily as a tubular toxin, it is capable of giving rise to a microangiopathic glomerular lesion similar to that in the hemolytic uremic syndrome. The classic model for immunologic glomerular lesion is Heymann nephritis, which produces a membranous glomerulopathy. Clinically, most drug mediated glomerulopathies also take the form of a membranous nephropathy, usually with a frank nephrotic syndrome. Among the more common offenders are penicillamine, gold salts used in rheumatoid arthritis, and captopril used in hypertension. The other common type of drug-related glomerulopathy occurs as part of a lupus-like syndrome induced by a variety of drugs, including hydralazine, procainamide, and penicillamine. All of these give rise to a variety of antibodies, most prominently antinuclear antibodies, and in the more severe cases there may be lupus-like glomerular lesions as well.
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PMID:Drug-associated glomerulopathies. 294 Jun 67

The influence of various immunoregulatory substances was studied in lymphocyte cultures derived from patients suffering from systemic lupus erythematosus (SLE) by using the model of spontaneous secretion of polyclonal immunoglobulin G (IgG)/immunoglobulin M (IgM) and anti-DNA autoantibodies. Compared with healthy donors, lymphocytes derived from patients with active SLE disease showed an elevated secretion of total IgG as well as anti-DNA-IgG in vitro, which was associated with an increase in the proportion of activated (HLA-class II +) T cells in their peripheral blood. Recombinant interferon-gamma increases the total IgG/IgM as well as anti-DNA-IgG/IgM secretion, which suggests that it has a possible role in the pathogenesis of SLE disease. Recombinant interleukin-2 and prostaglandin E2 normalize the high, spontaneous total IgG secretion, but elevate anti-DNA-IgG/IgM secretion. These results suggest that autoreactive B-cell clones are regulated differently in SLE patients. Cyclosporine inhibits total IgG/IgM secretion in all patients and anti-DNA-IgG/IgM secretion in six of eight patients. The possible therapeutic use of such immunomodulatory substances in SLE disease is discussed.
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PMID:The influence of interferon-gamma, interleukin-2, prostaglandin E2, and cyclosporine on the polyclonal and anti-DNA antibody secretion in lymphocyte cultures derived from patients with systemic lupus erythematosus. 311 53

Cyclosporine A (CyA) is being increasingly used as an immunosuppressive agent to treat various autoimmune diseases. A patient with systemic lupus erythematosus (SLE) receiving CyA after renal transplantation suffered a disease relapse associated with high serum CyA levels. Lowering of the CyA dose and the start of steroids resulted in a rapid improvement in her condition. Trials evaluating CyA for SLE should proceed with caution since under certain circumstances this drug may exacerbate disease activity.
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PMID:Relapse of systemic lupus erythematosus in a patient receiving cyclosporine A. 328 Jul 91


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