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)

The production of B cell-stimulating factors (BSF) by B cells in patients with systemic lupus erythematosus (SLE) was studied in vitro. B cells from SLE patients markedly proliferated and differentiated into Ig-producing cells by in vitro culture without any stimulation. The culture supernatant of these B cells contained BSF activity that stimulated Staphylococcus aureus Cowan I-treated normal B cells to proliferate and differentiate into Ig-producing cells. By a Percoll gradient density centrifugation, BSF-producing cells were enriched in the higher density fraction, but were reduced in the lower density fraction. The BSF also stimulated the proliferation and the differentiation of SLE B cells. By a Percoll gradient density centrifugation, SLE B cells responsive to the BSF were enriched in the higher density fraction, but were reduced in the lower density fraction. The Mr of the BSF was estimated as about 18,000 Da by Sephacryl S-200 column chromatography. The BSF fraction did not possess IL-2 and IFN activity, but possessed IL-1 activity, which stimulated murine thymocyte proliferative responses. The BSF activity was partially, but not completely, absorbed by an anti-IL-1 alpha antibody. Furthermore, the BSF possessed IL-4 activity, which induced not only the proliferative responses of normal B cells stimulated with B cell mitogens, but also the expression of low affinity Fc epsilon R/CD23 on normal B cells. The BSF also possessed IL-6 activity, which induced the proliferative responses of IL-6-dependent hybridoma cells, MH-60 BSF2. Moreover, human rIL-1, rIL-4, and rIL-6 stimulated SLE B cells. These results suggest that SLE B cells spontaneously produce the BSF such as IL-1 alpha, IL-4, and IL-6 and express their receptors on their surface, and the interaction between the BSF and their receptors stimulates SLE B cells to spontaneously proliferate and differentiate into Ig-producing cells as an autocrine mechanism.
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PMID:Production of B cell-stimulating factors by B cells in patients with systemic lupus erythematosus. 326 75

T cells from 18 untreated SLE patients produced significantly more B cell growth factor (BCGF) than did those from normal subjects. Those from SLE patients with active disease produced significantly more than did those from patients with inactive disease. The response to BCGF of SAC-stimulated B lymphocytes from SLE patients was higher than that of B lymphocytes from normal individuals. Similarly preactivated B cells from five of seven SLE patients also proliferated upon the addition of interleukin 1 (IL-1) whereas those of normal subjects did not. Simultaneous addition of IL-1 and BCGF had a synergistic proliferative effect on B cells from two of seven SLE patients but not on any of the controls. Interleukin 2 (IL-2) had no proliferative effect in either SLE or normal B cells. Supernatant fractions from T cells of seven of 10 patients with active SLE and three of 10 with inactive SLE induced more IgG production by CESS cells than did those of normal subjects indicating a higher production of B cell differentiation factor by SLE T cells than by those of controls. Our findings may explain the reported preactivation and predifferentiation of peripheral blood B cells from SLE patients and give insight into the mechanisms leading to the production of autoantibodies in this disease.
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PMID:Stimulating and differentiation factors for human B lymphocytes in systemic lupus erythematosus. 349 Sep 41

Leucocytic endogenous mediator is one of the activities ascribed to the cytokine or family of cytokines known as interleukin 1. In this study we have examined the ability of circulating blood leucocytes from patients with rheumatic diseases to produce this mediator in vitro. Leucocytic endogenous mediator production was found to be significantly decreased below normal values (mean 107 units, s.e.m. +/- 25) in systemic sclerosis (-6 units +/- 18), systemic lupus erythematosus (-25 units +/- 13), rheumatoid arthritis (-3 units +/- 13) and mixed connective tissue disease (-4 units +/- 40). A control group of ill patients with cancer produced 57 units +/- 8.
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PMID:Defective production of leucocytic endogenous mediator (interleukin 1) by peripheral blood leucocytes of patients with systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis and mixed connective tissue disease. 349 1

Splenocytes of MRL/l mice, one of the murine lupus strains, were found to produce a factor(s) which potentiates antibody formation. This factor was produced by splenocytes of young MRL/l mice and cell-sorting experiments by flow cytometry indicated that Thy 1.2+ cells were producing the factor. The approximate molecular weight of the factor was found to be 35,000-45,000 daltons and its pI value was between 3.3 and 3.8. It was also demonstrated that this factor is distinct from interferons, interleukins (IL-1, IL-2, IL-3) and B cell differentiation factors.
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PMID:A factor potentiating antibody formation spontaneously produced by splenic T cells of MRL/MP-lpr/lpr mice. 349 82

We measured the production of interleukin 1 (IL-1) and prostaglandin by adherent cells from patients with systemic lupus erythematosus (SLE). Compared to normal subjects, IL-1 production in the patients was lower but prostaglandin E1 production was higher. Furthermore, examination of monocyte subsets in patients with SLE using monoclonal anti-monocyte/granulocyte antibodies disclosed abnormal expression of membrane antigens on monocytes. It is speculated that aberration of monocyte function is related to impaired monokine production and that membrane antigens play a role in immunodysregulation in patients with SLE.
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PMID:Aberration of monokine production and monocyte subset in patients with systemic lupus erythematosus. 349 75

To explore the induction of monocyte/macrophage procoagulant activity in autoimmune disease, the BXSB murine model of systemic lupus erythematosus was studied. Splenic macrophage procoagulant activity rose coincident with age and the development of glomerulonephritis from 38 +/- 6 mU/10(6) macrophages at 1 mo to a maximum of 29,000 +/- 15,000 mU at 4 mo. Macrophages from 1-mo-old mice could be induced to express a 1,000-fold increase in monocyte/macrophage procoagulant activity when incubated with lymphocytes or lymphocyte supernatants from 5-mo-old mice. Plasma from 5-mo-old but not from 1-mo-old mice was able to induce the production of the lymphokine by cells from 1-mo-old animals. This lymphokine was not interleukin 1,2, or gamma interferon. We conclude that induction of monocyte/macrophage procoagulant activity parallels disease development in the male BXSB mouse, is dependent on the interaction between lymphocytes and plasma factors, and may be important in mediation of injury in lupus nephritis.
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PMID:Expression of macrophage procoagulant activity in murine systemic lupus erythematosus. 376 Jan 90

The objective of this study was to define some causes of the immunologic impairment characteristic of systemic lupus erythematosus. Blood mononuclear cells from 19 patients were stimulated to produce interleukin 1 and interleukin 2 and compared with controls. A severe defect in both IL 1 and IL 2 activity was observed. The low cytokine levels did not correlate with clinical or serologic activity of disease. These defects could not be explained by concurrent corticosteroid therapy. There was no correlation between a lower number of OKT4+ cells observed in these patients and the levels of IL 2 production, nor did removal of monocytes bring IL 2 to normal. Impaired IL 2 production could not be restored to normal by IL 1. The observed deficiency in these regulatory cytokines may therefore be a primary defect that is important in the pathogenesis of this disorder.
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PMID:Defective production of interleukin 1 and interleukin 2 in patients with systemic lupus erythematosus (SLE). 622 12

Interleukin-2 (IL-2) has been proven to be a defective element in immune regulation in systemic lupus erythematosus (SLE). However, its course in time is unknown. We studied its production and cellular response in the peripheral blood cells of 30 SLE patients and 12 healthy subjects. In addition, we studied the spontaneous and lipopolysaccharide (LPS) induced production of IL-1, which have been found to be, respectively, increased and lowered in untreated SLE patients. Patients were studied at the outset, when still untreated, and at 1, 2, 6, 12, 18, and 24 months. At the outset, 18 had active disease and 12 were in remission. The decreased proliferative response of T cells to IL-2 and the deficient production of IL-1 upon LPS induction became normal after 6 months treatment, whereas the expression of high affinity IL-2 receptors took 18 months to become normal and the deficient production of IL-2 took 2 years. Despite clinical remission, the decreased capacity of T cells to absorb IL-2 persisted for 2 years. The effect of various prednisone dosages on the measured variables was evaluated. With intermediate doses of prednisone (20-45 mg), we observed the largest improvement in IL-2 production and in IL-1 production upon LPS stimulation. Higher doses of prednisone reduced also the spontaneous production of IL-1 and resulted in an increase in the expression of CD25+ cells. The addition of low doses of cytotoxic drugs (oral cyclophosphamide or azathioprine) resulted in an improvement in the capacity to absorb IL-2 and a reduction in spontaneous IL-1 production.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Longitudinal study on the production of and cellular response to interleukin-2 in patients with systemic lupus erythematosus. 748 81

The objective of this study was to determine the effects of Methotrexate (MTX) on the development and the course of experimental murine SLE, as well as on the cytokine profile involved in the disease. SLE was induced in naive BALB/c female mice by injection of the human anti-DNA MoAb bearing a common idiotype (16/6 Id). Six weeks following immunization, when high levels of autoantibodies were demonstrated, the mice were treated with MTX (2 mg/kg once a week) for a period of 10 months. MTX treatment had no effect on 16/6 Id-induced autoantibody production. However, MTX treatment had beneficial effects on the clinical manifestations of the experimental disease (i.e. leucocyte counts, levels of protein in the urine and immune complex deposits in the kidneys). Thus, only 20% of 16/6 Id-immunized BALB/c mice that were treated with MTX had immune complex deposits in their kidneys compared with 100% of SLE-afflicted BALB/c mice that were not treated. We have observed a significant elevation in IL-1, tumour necrosis factor (TNF) and IL-10 secretion in BALB/c mice afflicted with experimental SLE. IL-2, IL-4, IL-6 and interferon-gamma (INF-gamma) levels were decreased in these mice compared with the levels detected in healthy controls. Treatment with MTX reversed the levels of all the above cytokines to normal levels observed in control mice. These studies demonstrate therapeutic effects of MTX on murine experimental SLE. The normal cytokine profile observed following treatment with MTX is suggested to play a role in the amelioration of the clinical manifestations of experimental SLE.
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PMID:Methotrexate treatment in murine experimental systemic lupus erythematosus (SLE); clinical benefits associated with cytokine manipulation. 762 94

Chloroquine can prevent photosensitivity reactions, but its mechanism of action is poorly understood. To investigate if the drug may interfere with inflammatory or immunological mechanisms of the UV-induced erythema of photosensitive patients, we studied the localization of chloroquine in the skin and its effect on the epidermal/dermal expression of IL-1, TNF-alpha, IL-6 and ICAM-1 and the occurrence of different lymphoid cells in normal skin and UVB-induced erythema in 8 patients with photosensitive discoid and systemic lupus erythematosus and 4 patients with polymorphic light eruption (PMLE), before and during chloroquine treatment. Using a specific monoclonal antibody against chloroquine, we found a strong granular staining pattern of mainly keratinocytes in all biopsy specimens from normal and erythematous skin during chloroquine treatment. In non-irradiated skin, T lymphocytes, macrophages and HLA-DR expressing cells were sparsely distributed within the dermis in similar amounts before and during chloroquine treatment. In UVB-induced erythema an increase in the number of these cells, mainly located in the dermal perivascular area, was seen before medication. During chloroquine treatment such cellular infiltration was reduced. ICAM-1 expression was detected on the endothelium of dermal vessels but not on keratinocytes. The accumulation of chloroquine in the epidermis and the decreased cellular infiltration in erythematous skin during chloroquine treatment indicate a local anti-inflammatory effect. This effect may be due to either unspecific UV-protective properties of the drug or to some specific downregulating action by chloroquine on keratinocyte function.
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PMID:In situ localization of chloroquine and immunohistological studies in UVB-irradiated skin of photosensitive patients. 765 84


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