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 synovial fluid in affected joints of rheumatoid arthritis (RA) patients contains many cells, in numbers strongly correlated with the severity of disease. As the disease worsens and the cell count increases, the polymorphonuclear leucocyte becomes the predominant cell type. Although the inflammatory cytokines interleukin 1 (IL-1) and tumour necrosis factor (TNF) have no direct neutrophil-attractant activity, they are both potent inducers of interleukin 8 (IL-8) in a variety of cell types. Chemotactic attraction of neutrophils is a major activity of IL-8. Examination of a number of synovial fluids showed that significant levels of IL-8 are present in a high proportion of RA cases (10 out of 17), at concentrations directly related to the number of cells in the joint, and to circulating C-reactive protein (CRP) levels. The cytokine is present only at background levels in other diseases accompanied by arthritic manifestations, including systemic lupus erythematosus (SLE) and induced arthritis. The progressive joint destruction seen in all cases where high IL-8 levels were measured, coupled with the neutrophil-rich cell count and the strong correlation between concentration of IL-8 and both serum CRP and cellular influx into the joint, is strongly suggestive of a pathogenic role for IL-8 in RA.
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PMID:Presence of NAP-1/IL-8 in synovial fluids indicates a possible pathogenic role in rheumatoid arthritis. 188 89

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

Renal vasculitis syndromes include particular characteristic changes in concentrations of some cytokines in plasma or urine. Preliminary results suggest that the systemic lupus erythematodes with affliction of the kidneys is specifically concomitted by the increase in IL-8, both in plasma and urine. ANCA-positive renal vasculitis syndromes appear to coincide with a typical increase in the synthesis of interleukin-6 in the kidneys. We suggest that the monitoring of individual cytokine levels in plasma and urine will enable to study in greater detail the immunopathogenesis of renal vasculitis syndromes and the extent of local production of cytokines which may cause further progression of renal lesions. (Fig. 4, Tab. 1, Ref. 10.).
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PMID:[Adhesion molecules and cytokines in vasculitides]. 862 Mar 22

Our study aims to determine whether anti-dsDNA exerts any effect on the gene expression of IL-8 or TGF-beta in cultured HUVEC. Both cytokines have angiogenic effect on endothelial cells. IgG was purified from 19 patients with SLE and from 19 healthy controls. Anti-dsDNA-depleted polyclonal IgG was also prepared from serum IgG of lupus patients by affinity chromatography with DNA cellulose column. Compared with either control IgG or anti-dsDNA-dep-IgG, HUVEC incubated with anti-dsDNA-containing-IgG expressed higher levels of IL-8 mRNA (p = 0.0001) and TGF-beta 1 mRNA (p = 0.0014). We demonstrated a significant increase in the percentage of cells with fragmented DNA in HUVEC incubated with anti-dsDNA-containing-IgG compared with those incubated with anti-dsDNA-dep-IgG, supporting the notion that anti-dsDNA may exert a direct apoptotic effect on cultured endothelial cells. Our study provides in vitro evidence that anti-dsDNA could play an important pathogenetic role in inducing inflammatory injury of vascular endothelium in SLE.
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PMID:Effect of anti-DNA autoantibodies on the gene expression of interleukin 8, transforming growth factor-beta, and nitric oxide synthase in cultured endothelial cells. 943 8

A 20-year-old woman with arthralgia, serositis, thrombocytopenia, proteinuria, muscle weakness, elevated creatinine kinase, and positive anti-Sm antibody was diagnosed as having polymyositis and systemic lupus erythematosus (SLE). She had persistent high temperature, sinus tachycardia, hyperhidrosis, mydriasis, visual disturbance, hallucination, and loss of consciousness. Levels of plasma adrenaline, noradrenaline, and dopamine and cerebrospinal fluid interleukin (IL)-6 and IL-8 were all high. A diagnosis of sympathetic hyperfunction accompanied by central nervous system (CNS) involvement in SLE was made parenteral. Pulse administration of high dose corticosteroid therapy was effective. This is the first reported case of a connective tissue disease with CNS involvement manifesting as sympathetic hyperfunction with high plasma catecholamine levels.
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PMID:Acute sympathetic hyperfunction in overlapping syndromes of systemic lupus erythematosus and polymyositis. 971 13

The chemokine is a new class of cytokine. Now, more than 30 members of chemokine superfamily and 15 members of chemokine receptors (CXCR1-4, CCR1-8, CX3CR, CCR) have been identified. They were shown to be involved in the inflammatory response. The chemokine is classified into four subgroups (CXC, CC, C and CX3C). The local production of IL-8, MCP-1 and RANTES in rheumatoid inflamed joints has been reported. The predominance of several chemokines in other collagen diseases, such as SLE, systemic sclerosis and myositis is also described. Therefore, the inhibition of chemokines or chemokine receptors might be novel targets for various human disease, including collagen diseases.
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PMID:[Chemokines and Chemokine receptors in collagen diseases]. 1007 91

In our previous reports, we found polyclonal anti-double-stranded DNA antibodies (anti-dsDNA) purified from patients with active systemic lupus erythematosus (SLE) exerted inhibitory effect on [3H]thymidine incorporation of human mononuclear cells (MNC). However, the other immunological effects of anti-dsDNA on the functions of MNC have not yet been reported. In this study, two monoclonal antibodies, 12B3 and 9D7, with different anti-dsDNA activity were evaluated for their effects on the expression and release of different cytokines from human MNC. We confirmed absence of endotoxin in the two monoclonal antibody preparations and the used medium as detected by Limulus amoebocyte lysate test. The mRNA expression and release of different cytokines including interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were measured. We found the two monoclonal anti-dsDNA not only dose-responsively suppressed the phytohaemagglutinin (PHA)-induced thymidine uptake of human MNC but stimulated the mRNA expression of IL-1beta, IL-6 and IL-8 in normal human MNC detected by reverse transcription-polymerase chain reaction (RT-PCR). Enzyme-linked immunosorbent assay (ELISA) measurement of cytokines in MNC culture supernatants revealed that anti-dsDNA enhanced IL-1beta, IL-8, TNF-alpha and IL-10 release from resting MNC. These effects of anti-dsDNA antibodies were not affected by polymyxin B, a potent binder and neutralizer of lipopolysaccharide (LPS). These in vitro studies suggest that anti-dsDNA possess a dual effect on normal human MNC: (a) to enhance the release of proinflammatory cytokines (IL-1beta, IL-8 and TNF-alpha) from MNC to augment inflammatory reaction; and (b) to polarize the immune reaction towards the T helper 2 (Th2) (increased IL-10 production) pathway. This unique effect of anti-dsDNA may play a role in lupus pathogenesis by augmenting inflammatory reactions and autoantibody production which are commonly found in patients with active SLE.
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PMID:Monoclonal anti-double-stranded DNA autoantibody stimulates the expression and release of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha from normal human mononuclear cells involving in the lupus pathogenesis. 1071 64

Tubulointerstitial nephritis is a less frequently recognized but important complication of systemic lupus erythematosus. We have investigated the cytokine beta2-microglobulin (beta2M) and Tamm-Horsfall glycoprotein (THG) excretions in the urine of systemic lupus erythematosus patients to identify indices for evaluation of tubulointerstitial inflammation in lupus nephritis (LN). Daily urine was collected from 15 patients with active LN, from 12 patients with inactive LN, and from 17 normal subjects. The amounts of soluble interleukin (IL) 2 receptor, IL-6, IL-8, beta2M, and THG in urine were measured. Beta2M and THG were regarded as indicators of proximal and distal renal tubule function, respectively. The urinary excretions of IL-6 and IL-8 were significantly higher in patients with active LN than in those with inactive LN and in normal individuals. The excretion of soluble IL-2 receptor in all three groups of subjects was not significantly different. On the other hand, the excretion of beta2M in patients with LN was significantly higher than that in normal individuals. The excretion of beta2M in patients with active or inactive LN was not significantly different. The THG excretion was lower in patients with active LN and tubulointerstitial inflammation as compared with patients with inactive LN or normal individuals. Six patients underwent pulse cyclophosphamide therapy during the course of experiments. Five of them showed a decrease in IL-8 and IL-6 excretions in urine after the treatment. The excretions of beta2M and THG in urine, in addition to IL-6 and IL-8, can reflect the renal inflammatory activity in patients with lupus tubulointerstitial nephritis as well as in those having lupus glomerulonephritis.
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PMID:Increased excretions of beta2-microglobulin, IL-6, and IL-8 and decreased excretion of Tamm-Horsfall glycoprotein in urine of patients with active lupus nephritis. 1086 35

Symptoms originating from central nervous system (CNS) are frequently occuring in patients with systemic lupus erythematosus (SLE). Reliable diagnostic markers for this condition are presently lacking. Importantly, CNS involvement in lupus patients is associated with increased morbidity and mortality. The aim of this retrospective evaluate was to study the diagnostic value of cerebrospinal fluid (CSF) cytokine levels in SLE patients with CNS involvement. 34 patients with SLE were hospitalized and investigated for the presence of CNS lupus. These patients were evaluated clinically and with magnetic resonance imaging (MRI) and CSF analyses, as well as with neuropsychiatric tests. 13 patients were found to have CNS lupus whereas another four of the patients fulfilled the criteria for CNS involvement but were excluded from this group due to other causes of CNS involvement. Lastly, in 17 SLE cases, the diagnosis of CNS lupus could not be confirmed. CSF levels of interleukin-6 (IL-6) and IL-8, as well as the CSF/serum IL-6 ratio, were elevated in the CNS lupus group, compared with the 17 SLE patients not fullfilling a diagnosis of cerebral lupus. Interestingly, follow-up of five patients being successfully treated for CNS lupus revealed profound decrease of intrathecal IL-6 levels. These results indicate that analysis of CSF cytokine levels, especially IL-6 and IL-8, may be useful in the diagnostics and possibly follow-up of SLE patients with cerebral lupus.
Lupus 2000
PMID:Intrathecal cytokines in systemic lupus erythematosus with central nervous system involvement. 1103 14

The revival of thalidomide began shortly after the drug was withdrawn from the market because of its teratogenic properties. Therapeutic effects of thalidomide were found accidentally in leprosy patients with erythema nodosum leprosum (ENL). Subsequent research widened the understanding of the activity of thalidomide, and with improved methodology and the augmented background knowledge of immunology it was possible to interpret the properties of thalidomide more coherently. Effects on tumour necrosis factor-alpha (TNFalpha) release play an important role in the ability of thalidomide to affect the immune system. Alteration of synthesis and release of cytokines such as interleukin (IL)-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 and interferon-gamma is involved in the complex mechanisms of thalidomide. Thalidomide targets leucocytes, endothelial cells and keratinocytes, affecting them in a different manner and at different cellular levels. Changes in the density of adhesion molecules alter leucocyte extravasation and the inflammatory response in the tissue involved. Several mechanisms for the teratogenic action of thalidomide are currently under review, but this mode of action of the drug still remains unclear and we review evidence-based hypotheses for the teratogenicity of thalidomide. Thalidomide shows significant clinical impact in several diseases such as ENL in lepromatous leprosy, chronic graft-versus-host disease, systemic lupus erythematosus, sarcoidosis, aphthous lesions in HIV infection, wasting syndrome in chronic illness, inflammatory bowel disease, multiple myeloma and some solid tumours. In 1998 the US Food and Drug Administration approved thalidomide exclusively for the treatment of ENL, and strict conditions were stipulated for its use in order to prevent teratogenic adverse effects. However, despite the promising findings of thalidomide at the molecular level, namely its anti-TNFalpha properties and its intercalation with DNA, and activity in clinical trials, there is still a great need for more intensive research.
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PMID:Theoretical basis for the activity of thalidomide. 1160 49


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