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 examined cerebrospinal fluid (CSF) samples from 12 patients with SLE and active central nervous system (CNS) involvement for their levels of the following cytokines: interleukin-1 (IL-1) by means of two different assays--the IL-1 responsive murine cell line LBRM 33-la5 and an ELISA for IL-1 alpha; IL-2 by means of the CTLL cell line responsive to it; and interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF) both determined by a specific ELISA. We found that SLE CSF had significantly higher levels of IL-1 and IL-6 than did those obtained at surgery from eight controls without inflammatory neurologic disease. IL-2 and TNF were not detectable in any of the CSF samples. We also studied the status of activation in CSF T cells using monoclonal antibodies against early (anti-IL-2R (CD25) and anti-transferrin (CD71)), late (anti-T10) and very late (anti-VLA-1) activation antigens, and found increased percentages of T10-bearing (18 +/- 2 vs 3 +/- 0.7%) and VLA-1-bearing T cells (12 +/- 2 vs 0.7 +/- 0.2%) in SLE patients as compared to controls (both P < 0.01). Levels of IL-1 and IL-6 correlated with T10 and those of IL-1 correlated also with VLA-1. Markers of early T-cell activation did not differ in SLE and control CSF. Because of these findings we analysed the effect of recombinant IL-1, IL-6 or normal CSF on normal T cells and found that they did not induce the expression of activation markers.(ABSTRACT TRUNCATED AT 250 WORDS)
Lupus 1992 Feb
PMID:Interleukin-1 and interleukin-6 activities are increased in the cerebrospinal fluid of patients with CNS lupus erythematosus and correlate with local late T-cell activation markers. 130 62

We have analyzed the roles of tumor necrosis factor alpha (TNF-alpha) in human systemic lupus erythematosus (SLE) and murine models of lupus as well as in type 1 diabetes in NOD mice. These studies suggest an important role for TNF-alpha in the pathogenesis of autoimmune disease. Rather than being involved mainly in the effector arm of the inflammatory process of autoimmune organ destruction, our data suggest a primary involvement in some of the basic mechanisms of the autoimmune process. Evidence has been presented that emphasizes the possibility of the involvement of this cytokine in the genetic predisposition to SLE. The data may imply that the effect of TNF on the immune system may be more relevant to the pathogenesis of the autoimmune disease than direct local effects at some target organs. Based on the data presented, one should be cautious in extrapolating the effects of this cytokine in various in vitro systems to the in vivo situation.
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PMID:Studies on the role of tumor necrosis factor in murine and human autoimmunity. 150 8

Recombinant tumor necrosis factor alpha (TNF-alpha) administration significantly delayed the development of lupuslike nephritis in the New Zealand black x New Zealand white (NZB x NZW)F1 and to a lesser extent in the MRL-lpr/lpr model systems. TNF-alpha treatment was effective when treatment was initiated at 2, 3, or 4 months of age but was ineffective if initiated as late as 6.5 months of age. Treatment of (NZB x NZW)F1 mice for 3 months was more effective than treatment continued for 6 months. Anti-TNF-alpha antibodies did not develop in these mice. Flow microfluorometry analysis showed no major effects on B, T, or monocyte cell population in cells from the peritoneum, spleen, lymph node, and thymus. A decrease in class II Ia expression on macrophages in the peritoneum of TNF-alpha-treated mice was noticed. A correlation between the level of TNF-alpha inducibility in vitro and the effect of TNF-alpha administration in vivo could be shown. Although a limited polymorphism could be shown by restriction fragment length polymorphism, using an amplified (AC)n microsatellite located in the 5' regulatory region of TNF-alpha, a much more extensive interallelic polymorphism was found. The AC microsatellite allele found in NZW mice was unique and different from other lupus strains and nonautoimmune strains. These results have possible implications to the pathogenesis of systemic lupus erythematosus.
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PMID:Tumor necrosis factor alpha in murine systemic lupus erythematosus disease models: implications for genetic predisposition and immune regulation. 168 13

In view of recent data demonstrating defective production of tumor necrosis factor alpha (TNF cachectin) in murine autoimmune lupus nephritis, we studied the serum levels of TNF in 22 patients with systemic lupus erythematosus (SLE), using a specific radioimmunoassay. Patients with SLE had either normal or slightly elevated levels of TNF when compared with healthy control subjects. All 5 SLE patients with concomitant infections had elevated levels of TNF; those with systemic bacterial infection had markedly raised levels (median 260 pg/ml; normal less than 40). These results show that SLE in humans is not associated with a depressed level of circulating TNF, and that in SLE patients with infection, the level of TNF in the circulation increases in a manner similar to that in other subjects.
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PMID:Tumor necrosis factor in the serum of patients with systemic lupus erythematosus. 292 50

The role of tumor necrosis factor alpha (TNF-alpha) was examined in biopsy-proven glomerulonephritis by immunohistochemistry, in situ hybridization, immunogold electron microscopy, immunoassay in serum and urine, and urinary immunoblot. Striking glomerular capillary wall and visceral glomerular epithelial cell TNF-alpha protein staining was observed in all cases of membranous nephropathy and membranous lupus nephropathy. Staining was less frequently observed in crescentic glomerulonephritis and in isolated cases of other histological subtypes of glomerulonephritis, usually in association with glomerular macrophages. By immunogold electron microscopy TNF-alpha was localized in membranous nephropathy within the visceral glomerular epithelial cells, and also in the glomerular basement membrane, especially in relation to immune deposits. In situ hybridization localized TNF-alpha mRNA exclusively to glomerular epithelial cells in all biopsies with membranous morphology but not in other histological subtypes. Concentrations of TNF-alpha were significantly increased compared with normal controls in the urine of patients with membranous nephropathy and with crescentic glomerulonephritis. The expression of TNF-alpha by glomerular epithelial cells exclusively and universally in biopsies showing a membranous morphology strongly suggests this cytokine has a role in the pathogenesis of membranous nephropathy.
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PMID:Tumor necrosis factor-alpha is expressed by glomerular visceral epithelial cells in human membranous nephropathy. 777 83

Photopheresis is an apheresis-based therapy that is currently available at approximately 70 medical centers worldwide. Recent evidence indicates that extracorporeal photopheresis can significantly prolong life as well as induce a 60-75% response rate among individuals with advanced cutaneous T-cell lymphoma (CTCL). Moreover, a 10-15% cure rate, in response to photopheresis alone, or in combination with interferon-alpha, has been obtained at our institution. These complete responses have been characterized by the complete disappearance of morphologically atypical cells from the skin and blood. Southern blot analysis of peripheral blood specimens has also confirmed the indefinite disappearance of the malignant T-cell clone from the blood of patients with complete responses. Current immunological data obtained from in vitro human studies and from animal models suggest that the basis for the responses of CTCL patients are related to activation of treated macrophages resulting in release of cytokines, including substantial levels of tumor necrosis factor alpha (TNF-alpha), and perhaps, to the induction of anticlonotypic immunity directed against pathogenic clones of T lymphocytes. In addition to the treatment of CTCL, a potential role for photopheresis in the therapy of autoimmune disease has been suggested by recent pilot studies of pemphigus vulgaris, rheumatoid arthritis, and systemic lupus erythematosus. Furthermore, a randomized, single-blinded trial involving 79 patients with early onset, aggressive systemic sclerosis suggested that photopheresis could benefically affect the course of the cutaneous thickening in this form of the disease. Lastly, two independent pilot studies of cardiac transplantation have indicated that photopheresis can reverse acute cardiac allograft rejection and potentially suppress ongoing chronic rejection. Randomized, controlled trials for these new indications for photopheresis therapy are currently in the early stages of implementation.
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PMID:Review of immunomodulation by photopheresis: treatment of cutaneous T-cell lymphoma, autoimmune disease, and allograft rejection. 788 25

We have investigated the significance of tumor necrosis factor alpha (TNF-alpha) polymorphism in relation to systemic lupus erythematosus (SLE) and autoantibody production. Typing of HLA-B, -DR and TNF was performed in 81 Caucasian SLE patients and 168 Caucasian controls. The presence of anti-Ro and anti-La antibodies was also determined in patients. The frequency of the TNF2 allele increased in SLE compared with controls [0.24 vs. 0.17, p = 0.04, odds ratio (OR) = 1.6], as did HLA-DR3 (0.25 vs. 0.13, p < 0.01, OR = 2.3) and HLA-B8 (0.23 vs. 0.15, p = 0.02, OR = 2). Although HLA-DR3 showed the strongest disease association, we could not demonstrate association of HLA-DR3 or TNF2 with SLE independently of each other. Within SLE a much stronger association of TNF2 was seen with autoantibody production: anti-Ro antibody (0.39 vs. 0.16, p < 0.001, OR = 3.4) and anti-La antibody (0.43 vs. 0.19, p < 0.001, OR = 3.2). When analyzed independently of each other, however, HLA-DR3 remained significantly associated with autoantibodies, while TNF2 did not. These data suggest that on the B8-DR3 haplotype, TNF-alpha polymorphism may play a role in SLE susceptibility, but it is not primarily associated with autoantibody production.
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PMID:A genetic association between systemic lupus erythematosus and tumor necrosis factor alpha. 802 May 56

The contents of tumor necrosis factor alpha (TNF alpha) was measured by enzyme immunoassay in the serum from 43 healthy donors against 49 patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). In all the donors the cytokine did not reach 50 pg/ml, in SLE and RA running actively TNF alpha levels got elevated in the absence of previous long-term immunocorrection. Under the treatment effect blood levels of the cytokine fell in inhibition of the autoimmune process. Resistant to therapy patients with active rheumatic process kept for a long period on steroids exhibited TNF alpha concentrations less than 50 pg/ml. Low activity of the process and no need in corrective therapy were attended by normal TNF alpha content. The findings urge further efforts in the search for new approaches to SLE and RA treatment.
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PMID:[The level of the tumor necrosis factor in the blood serum of patients with systemic lupus erythematosus and rheumatoid arthritis]. 803 8

Cerebrospinal fluid (CSF) from patients with a variety of central nervous system (CNS) disorders was assayed for cytokines, prostaglandins, and autoantibodies. CSF interleukin-6 (IL-6) in patients with CNS infection (374.24 +/- 92.61 pg/mL) and neuropsychiatric systemic lupus erythematosus (NP-SLE) (71.40 +/- 5.89 pg/mL) were significantly higher than in patients with CNS inflammation (33.92 +/- 29.36 pg/mL) or controls (non-inflammatory CNS diseases) (4.35 +/- 3.00 pg/mL). Interleukin-1 beta, interferon alpha, and tumor necrosis factor alpha were undetectable in these samples: CSF prostaglandin E2 (PGE2) also exhibited similar patterns as IL-6. CSF immunoglobulin G (IgG) in patients with NP-SLE (8.84 +/- 1.80 mg/dL) was much higher than in patients with CNS infection (4.65 +/- 3.09 mg/dL), CNS inflammation (2.54 +/- 1.24 mg/dL), or controls (2.11 +/- 1.03 mg/dL). CSF autoantibodies against calf thymus antigens were present in patients with NP-SLE but not in patients with CNS infection as demonstrated by immunoblot. These results suggest that high IL-6 and PGE2 in CSF favors the diagnosis of CNS infection, while modestly elevated IL-6, high IgG, and autoantibodies against calf thymus antigens in CSF are the features of NP-SLE.
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PMID:Cerebrospinal fluid interleukin-6, prostaglandin E2 and autoantibodies in patients with neuropsychiatric systemic lupus erythematosus and central nervous system infections. 816 38

IgG antiendothelial antibodies (IgG AEA), as measured by enzyme-linked immunosorbent assay, could be detected in serum samples of 38 out of 41 patients with systemic lupus erythematosus. Incubation of endothelial cells (EC) with interleukin-1 alpha (IL-1 alpha), in contrast to incubation with interferon gamma or tumor necrosis factor alpha, resulted in an enhanced IgG AEA binding. Immunoblotting revealed reactivity of AEA against a variety of EC antigens. The upregulation of IgG-AEA-binding reactivity to IL-1 alpha-stimulated EC was due to binding to antigens that were already expressed by unstimulated EC. The IgG-binding reactivity to both IL-1 alpha-stimulated and unstimulated EC was significantly higher in the serum of patients with joint or skin abnormalities as compared with patients without these manifestations. These data suggest that upregulated binding of IgG to EC induced by IL-1 alpha may play a role in immune vascular damage.
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PMID:Antiendothelial cell antibodies in systemic lupus erythematosus: enhanced antibody binding to interleukin-1-stimulated endothelium. 819 56


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