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)

Levels of tumor necrosis factor/cachectin (TNF alpha) assessed by ELISA were similar in the supernatant of cultures from peripheral blood mononuclear cells (PBMC) from either active or inactive systemic lupus erythematosus (SLE) patients and controls stimulated with mitogen alone. When PBMC were stimulated with mitogen plus phorbol 12-myristate-13-acetate (PMA), the amount of TNF alpha was significantly decreased in culture supernatants from active patients or from the entire group of SLE patients studied. However, spontaneous synthesis of TNF alpha in nonstimulated cultures was increased in the SLE patients. Interferon-gamma (IFN-gamma) enhanced TNF alpha synthesis in cultures from either SLE patients or controls stimulated by concanavalin A (Con A) alone, but depressed the high production of TNF alpha by normal PBMC stimulated with Con A plus PMA. IFN-gamma enhanced TNF alpha production in response to Con A plus PMA in 2 of 3 SLE patients.
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PMID:Production of tumor necrosis factor/cachectin by peripheral blood mononuclear cells in patients with systemic lupus erythematosus. 279 23

Tissue localization of tumor necrosis factor (TNF alpha) was examined in synovial tissues from 10 patients with active rheumatoid arthritis (RA) and three osteoarthritis controls using both monoclonal and polyclonal antibodies to TNF alpha and immunoperoxidase technique. No prominent staining for TNF alpha was noted in any of the osteoarthritis non-inflammatory synovial samples; however, six out of 10 RA synovial tissues displayed strongly positive tissue distribution of TNF alpha epitopes particularly within synovial lining cells, and interstitial monocyte/macrophage cells within inflammatory infiltrates. The amounts of TNF alpha visualized within synovial lining cells appeared to parallel the extent of inflammatory cell collections within the rheumatoid synovial tissues examined. Similar studies using renal biopsy tissues from seven patients with Systemic Lupus Erythematosus (SLE) nephritis (including diffuse proliferative nephritis, nephrotic syndrome, focal glomerulonephritis, and membranous nephritis) showed no tissue localization of TNF alpha. These findings emphasize that a potent lymphokine (TNF alpha), which may be important in the underlying inflammatory process, appears to be localized and perhaps produced by synovial lining cells within active RA synovial tissues.
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PMID:Synovial localization of tumor necrosis factor in patients with rheumatoid arthritis. 307 63

Neurotrophins (NTs), including nerve growth factor (NGF), are multifunctional: in addition to their well-characterized neurotrophic functions they are known to regulate and to be regulated by cytokines, components of the immune system. In line with this we have found expression of a functional trk proto-oncogene, constituting the signal transducing-receptor for NGF, on monocytes/macrophages, lymphocytes and basophils. Moreover, NGF synthesis is regulated by a cytokine cascade including inflammatory mediators such as interleukin-1 and tumor necrosis factor-alpha. The fact that NGF levels are markedly elevated in cerebrospinal fluid of patients with multiple sclerosis and in serum of patients with systemic lupus erythematosus strongly indicates a role for NGF in immunopathology as well as in normal immune function.
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PMID:Neurotrophins and cytokines--intermediaries between the immune and nervous systems. 757 71

Systemic lupus erythematosus (SLE) is a chronic inflammatory condition characterised by arthritis, cutaneous rash, vasculitis, and involvement of central nervous system, renal and cardiopulmonary manifestations. Abnormalities in the cytokine network is believed to be involved in the pathobiology of this condition. The n-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can suppress T-cell proliferation and the production of interleukin-1, interleukin-2, and tumor necrosis factor by these cells both in vitro and in vivo. Oral supplementation of EPA and DHA induced prolonged remission of SLE in 10 consecutive patients without any side-effects. These results suggest that n-3 fatty acids, EPA and DHA, are useful in the management of SLE and possibly, other similar collagen vascular diseases.
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PMID:Beneficial effect of eicosapentaenoic and docosahexaenoic acids in the management of systemic lupus erythematosus and its relationship to the cytokine network. 782 35

CD30 is a member of the tumor necrosis factor (TNF)/nerve growth factor (NGF) receptor superfamily, and was originally described as a marker of Hodgkin's and Reed-Sternberg cells in Hodgkin's lymphoma. CD30 is preferentially expressed on CD4+ and CD8+ T-cell clones that produce T helper 2 (Th2)-type cytokines, and is also released in a soluble form by these cells. Elevated serum levels of soluble (s)CD30 have been found in some conditions in which a pathogenic role for Th2 cells has been suggested, such as atopy, Omenn's syndrome, systemic lupus erythematosus, as well as following infection with measles virus or human immuno-deficiency virus (HIV). Here, Gianfranco Del Prete and colleagues suggest a complex and fascinating link between the expression and release of CD30, and the immunopathogenesis of HIV infection.
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PMID:CD30, Th2 cytokines and HIV infection: a complex and fascinating link. 788 70

Although systemic lupus erythematosus (SLE) is known to be positively associated with certain major histocompatibility complex (MHC) class I and/or class II antigens, it is not clear whether the MHC genes are the predisposing genes of the disease rather than markers for other closely linked gene(s). Because of the involvement of tumor necrosis factor (TNF) in the inflammation process and localization of the TNF genes in the proximity of the HLA-B locus, we studied the restriction fragment length polymorphism (RFLP) of the TNF-alpha and -beta genes in 20 SLE patients and 23 normal individuals using restriction endonuclease NcoI. The frequency of a 5.5 kb NcoI fragment from SLE patients was significantly higher than that from normal controls. This result suggests that the polymorphic TNF genes may be involved in the pathogenesis of SLE.
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PMID:Restriction fragment length polymorphism (RFLP) analysis in the TNF genes of patients with systemic lupus erythematosus (SLE). 790 14

This study was designed to explore the prevalence and clinical significance of elevated antiphospholipid antibodies (APA) titres in patients affected by acute myeloid leukemia (AML) and high-grade non-Hodgkin's lymphoma (NHL). We also analyzed possible correlations with circulating levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and the soluble form of the receptor for interleukin-2 (sIL-2r). Nineteen patients with de novo AML and 14 patients with newly-diagnosed NHL were investigated. Tests for APA included the measurement of anticardiolipin antibodies (ACA) with a solid-phase immunoassay, and the detection of the lupus-like anticoagulant (LA) activity. Five patients with AML (26.3%) and 5 patients with NHL (35.7%) presented elevated APA at diagnosis, as compared to 3 of 174 persons of the control group (p < 0.0001). APA titres became normal in all patients responding to treatment, whereas non-responders retained elevated levels. In addition, 6 patients (4 with AML and 2 with NHL), who had normal APA at diagnosis and were either refractory to treatment or in relapse, subsequently developed LA and/or ACA positivity. At presentation, the mean levels of IgG- and IgM-ACA in patients were not significantly different from controls, and concordance between ACA and LA results reached just 30%. With regard to the clinical course, we were not able to detect any statistically significant difference between patients with normal and elevated APA. Pretreatment concentrations of IL-6 and TNF-alpha in AML, and sIL-2r in NHL were found significantly elevated compared to controls (p = 0.003, p = 0.009 and p = 0.024 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antiphospholipid antibodies: prevalence, clinical significance and correlation to cytokine levels in acute myeloid leukemia and non-Hodgkin's lymphoma. 811 79

Lupus-like autoimmunity in (NZB x NZW)F1 mice is frequently marked by the development of a severe and fatal renal disease. Genes from both NZB and NZW parents are required for the full expression of disease. We applied a mapping technique based on polymorphism in simple sequence repeats to the analysis of (NZB x NZW)F1 x NZW backcross mice to determine the NZB genetic contribution to disease. The results show that a single NZB locus or tightly linked group of loci on the distal part of chromosome 4 provides the strongest association with renal disease and death. This locus, designated here as nba-1 (New Zealand Black autoimmunity), lies distal to the locus elp-1, 60-70 centimorgans from the centromere. It is of interest that a gene encoding a receptor for tumor necrosis factor maps to the vicinity of this disease-associated gene.
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PMID:Genetic analysis of the NZB contribution to lupus-like autoimmune disease in (NZB x NZW)F1 mice. 817 Oct 35

Previous studies in our laboratory demonstrated an altered immuno-endocrine feedback communication via the hypothalamo-pituitary-adrenal (HPA) axis, which may be an important modulatory factor in the development of spontaneous autoimmune thyroiditis in Obese strain (OS) chickens. These birds show a significantly lower, or even absent, increase in serum glucocorticoid levels in response to an intravenous injection of antigen or conditioned medium (CM) from mitogen-stimulated spleen cells known to contain glucocorticoid-increasing factors (GIFs), notably interleukin-1 (IL-1). The present study was aimed at investigating this feedback regulation in animal models with spontaneous systemic autoimmune diseases, such as the UCD-200 chicken, which serves as a model for human scleroderma, and various murine lupus models. In contrast to OS chickens, UCD-200 chickens displayed a nearly normal plasma corticosterone surge in response to CM, and IL-1 was again identified as the primary GIF in CM. Recombinant IL-1 also induced a drastic increase in plasma corticosterone levels in various strains of normal mice. A similar increase was observed in the bacterial lipopolysaccharide-resistant C3H/HeJ strain, thus excluding the possibility of bacterial endotoxin contamination. However, in young lupus-prone (NZB/W)F1 and MRL/MP-lpr mice, a significantly lower increase in plasma corticosterone levels was observed after injection of recombinant IL-1, suggesting a deficient immuno-endocrine communication via the HPA loop in this instance as well. Detailed studies to identify further cytokines with GIF activity in the avian and murine systems showed that both IL-6 and tumor necrosis factor-alpha could induce increased plasma corticosterone levels in mice, but not in chickens. IL-3, IL-8, transforming growth factor-beta, interferon-gamma and granulocyte-macrophage colony-stimulating factor were devoid of GIF activity in both chickens and mice.
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PMID:Disturbed immuno-endocrine communication via the hypothalamo-pituitary-adrenal axis in autoimmune disease. 821 76

This report represents follow-up observations of a unique long-term study of patients on procainamide (PA) for various cardiac arrhythmias. Serologic and clinical evaluations associated with drug-related autoimmunity were assessed and patients were characterized for factors postulated to influence susceptibility to autoimmunity, including acetylator phenotype, oxidative metabolism of PA, HLA class profile, and production of interleukin-1 (IL-1) and tumor necrosis factor (TNF). Fifty-two percent had IgM and 70% IgG antibodies to total histones; 67% had IgG antibodies to histone H2A/H2B. Patients were equally divided between fast and slow acetylators. N-oxidative metabolism of PA was indicated by the presence of urinary nitroprocainamide, which correlated with elevated titers of antihistone antibodies. There was a significant incidence of the DQw7 split of DQw3 in PA patients when compared to controls, and the frequency of antibodies to total histones and H2A/H2B was significantly increased in the DQw7 patients. C4A*QO and C4B*QO alleles were more frequent in the PA patients than in controls. IL-1 and TNF production was not different in patients compared to controls. These data suggest that certain genetic factors may serve as markers for PA-related autoimmunity.
Lupus 1993 Apr
PMID:Genetic, immunologic and biotransformation studies of patients on procainamide. 833 41


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