Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because of the high morbidity and mortality in patients with bacterial arthritis, rapidly and correctly diagnosing this critical condition is a challenge to emergency clinicians. Synovial fluid samples were obtained from 75 patients with arthritis disorders who presented to an emergency service, and levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) were measured. Twenty patients with culture-proven bacterial arthritis had higher levels of synovial TNF-alpha than patients with osteoarthritis or with inflammatory arthritis, including gouty arthritis, rheumatoid arthritis, reactive arthritis, and lupus arthritis. There was a good sensitivity for synovial TNF-alpha level in diagnosing patients with bacterial arthritis. Nearly 100% of patients with bacterial arthritis had elevated synovial TNF-alpha levels. However, synovial IL-1 beta and IL-6 levels failed to discriminate bacterial arthritis from other inflammatory arthritis. Measurement of synovial TNF-alpha level may be useful as a diagnostic aid in emergency patients with bacterial arthritis disorders.
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PMID:Measurement of synovial tumor necrosis factor-alpha in diagnosing emergency patients with bacterial arthritis. 937 40

The psychiatric and cognitive condition of a patient with lupus psychosis was evaluated. Using a device that detects the corneal reflection of infrared light, the patterns of eye tracking movements were recorded before the onset of lupus psychosis, after remission, and again 1 year later. Electroencephalographic findings and cerebrospinal fluid levels of both interferon alpha and interleukin-6 were also obtained longitudinally. Electroencephalographic findings and clinical signs were correlated to the levels of interferon alpha in cerebrospinal fluid. Analysis of exploratory eye movements revealed marked decreases in the number of eye fixation, mean eye-scanning length and total eye-scanning length. Even though the lupus psychosis resolved and the electroencephalographic findings became normal, the eye movement patterns showed remaining deterioration. It was concluded that analysis of exploratory eye movements in patients with systemic lupus erythematosus may be useful in diagnosing lupus psychosis, and may also present a diagnostic clue to subclinical lupus psychosis.
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PMID:Analysis of exploratory eye movement in a patient with lupus psychosis. 980 82

Anti-CD4 antibodies have been recently introduced into the therapy of various autoimmune diseases, among them systemic lupus erythematosus (SLE). Their modes of action are not yet fully understood. Interference with cytokine release may be one possible mechanism. Therefore, the effects of anti-CD4 antibodies on the cytokine release of IL-6 (interleukin-6) and TNF-alpha (tumor necrosis factor alpha) were investigated in a whole blood culture system. Basal and phytohemagglutin/lipopolysaccharide (PHA/LPS)-stimulated cytokine patterns were compared to cytokine release after the addition of anti-CD4 antibodies (MAX.16H5) or methylprednisolone in short time whole blood cell culture systems from 12 patients with active SLE, 23 patients with inactive SLE and 12 healthy volunteers. TNF-alpha and IL-6 concentrations were determined in the supernatants by ELISA. High disease activity correlated with an increased production of proinflammatory cytokines. Cell cultures of patients with inactive SLE showed a diminished capacity to respond to mitogenic stimulation. Anti-CD4 antibodies added in vitro suppressed significantly the unstimulated production of IL-6 (P<0.02) in the cell cultures of patients with active SLE and in the PHA/LPS-stimulated cell cultures from both groups of SLE patients (both P<0.001) and healthy volunteers (P<0.01). However, MAX.16H5 did not affect the release of TNF-alpha. In control samples methylprednisolone considerably reduced stimulated and unstimulated IL-6 and TNF-alpha production in all SLE patients, irrespective of the disease state, and in all healthy controls. These data indicate that the proinflammatory cytokines are involved in the pathogenesis of SLE. It is assumed that anti-CD4 antibodies, which can be effective in the treatment of highly active lupus patients, may act via their influence on cytokine release. The decrease of the proinflammatory cytokines IL-6 under therapy with MAX.16H5 could explain the observations of clinical trials and animal studies which showed a reduction of inflammatory parameters and diminished production of autoantibodies following treatment with anti-CD4 antibodies.
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PMID:Effects of anti-CD4 antibodies on the release of IL-6 and TNF-alpha in whole blood samples from patients with systemic lupus erythematosus. 1060 44

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.
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PMID:Intrathecal cytokines in systemic lupus erythematosus with central nervous system involvement. 1103 14

The onset of autoimmunity in lupus-prone mice is accompanied by a constellation of behavioral deficits, termed Autoimmunity-Associated Behavioral Syndrome (AABS). In particular, a spontaneous increase in serum interleukin-6 (IL-6) levels in five-week old MRL-lpr mice coincides temporally with blunted responsiveness to sucrose and excessive immobility in the forced swim test. These relationships, along with evidence that sucrose intake drops after systemic IL-6 overexpression is induced in healthy mice, have led to the hypothesis that sustained elevation in serum IL-6 also induces other aspects of AABS. This hypothesis is tested by comparing the behavioral profiles of healthy mice infected with Ad5mIL6 adenovirus (2 x 10(8) pfu of virus/mouse i.p.) with those of animals infected with control Ad5 virus. This methodology was used to achieve high circulating levels of IL-6, to overcome the problem of its short half-life, and to avoid the stressful effects of repeated injections. The Ad5mIL6 infection (known to induce excessive IL-6 levels over five days) transiently reduced food, water, and sucrose intake, as well as rectal temperature in MRL +/+ and AKR/J mice. Although the level of locomotor activity did not decline, Ad5mIL6-infected AKR/J mice demonstrated less novel object exploration. Performance in the step-down, plus-maze, and spontaneous alternation tests were disturbed to various degrees in all infected animals. The present results suggest that prolonged exposure to circulating IL-6 primarily impairs ingestive behavior, likely reflecting enhanced catabolism. The inability of circulating IL-6 to alter other aspects of behavior supports the hypothesis that multiple immuno-neuroendocrine mechanisms contribute to the pathogenesis of AABS.
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PMID:Behavioral effects of infection with IL-6 adenovector. 1125 78

Lipid-lowering drugs have been shown to have profound actions beyond modulation of lipid profiles. Statins have been shown to reduce the levels of pro-inflammatory cytokines and markers of acute phase response including C-reactive protein and serum amyloid A. Fibrates have also shown to reduce interleukin-6 levels. Both groups of drugs seem to act through a peroxisomal proliferating activating receptor alpha mechanism to achieve these actions. In lupus, there is profound activation of cytokine production and the acute phase response and a markedly increased risk for the development of atherosclerosis. The role of lipid-lowering drugs in the management of both the acute and chronic sequelae of lupus needs to be explored.
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PMID:Lipid-lowering drugs in lupus: an unexplored therapeutic intervention. 1131 59

The lack of phenotype/genotype association in X-linked adrenoleukodystrophy (X-ALD) has prompted the search for disease modifying factors. We previously demonstrated increased serum antibody responses against myelin oligodendrocyte glycoprotein (MOG) in various clinical phenotypes of X-ALD allowing speculations that myelin specific humoral immune responses might be involved in phenotype generation of X-ALD. In the present study, we investigated the possible association of (1) a naturally occurring variable number tandem repeat (vntr) polymorphism (C allele) in the 3' flanking region of the interleukin-6 gene (IL-6), previously demonstrated to modify the course of Alzheimer's disease, systemic lupus erythematodes and Multiple Sclerosis (MS), (2) a tetranucleotide repeat polymorphism (TAAA)(n) in the 3' flanking region of the MOG gene and (3) HLA class II alleles with adult clinical phenotypes and serum antibody responses to MOG in 70 adult X-ALD patients. HLA class II alleles, (TAAA)(n) MOG gene polymorphisms, and IL-6 C allele were not associated with clinical phenotypes. Anti-MOG antibodies were detectable in 17/54 X-ALD patients (31.5%). Anti-MOG antibodies were associated with the 226 bp (TAAA)(n) MOG gene polymorphism but not with distinct clinical phenotypes.
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PMID:Genetic variations and humoral immune responses to myelin oligodendroglia glycoprotein in adult phenotypes of X-linked adrenoleukodystrophy. 1257 35

We report a case of central nervous system (CNS) lupus showing peculiar findings on cranial magnetic resonance imaging (MRI) with remarkable improvement after corticosteriod therapy. The patient was a 28-year-old woman, admitted to our hospital with severe fever, general malaise, and facial edema on June 4, 2001. After admission, she was diagnosed with systemic lupus erythematosus (SLE). On June 6, she showed diplopia at a distance, and on June 10, she suddenly became unconscious and developed general convulsions. Cranial MRI showed asymmetrical, multifocal, high signal intensity lesions on T2-weighted image (T2-WI) and low signal intensity on T1-weighted image (T1-WI). These lesions were primarily present in the subcortical white matter, with some detected in the overlying cerebral cortex. Gadolinium (Gd)-DTPA enhanced T1-WI showed marked leptomeningeal enhancement overlying the lesions on T1-WI and T2-WI. Apparent diffusion coefficient image (ADCI) showed high signal intensity in the surrounding areas of the T1-WI and T2-WI lesions, and low signal intensity in the central areas of the lesions. Diffusion weighted image (DWI) showed high signal intensity in the central areas of the low signal intensity on ADCI. Cerebrospinal fluid (CSF) examination revealed albuminocytologic dissociation (cell counts of 2/microliter and protein level of 108 mg/dl). CSF IgG index was elevated to 1.152 (normal < 0.7) and interleukin-6 (IL-6) activity to 27.2 pg/ml (normal < 4.0). On June 10, Intravenous administration of high-dose methylprednisolone (1,000 mg/day for 3 days) was started to treat CNS lesions of SLE. Her CNS manifestations, CSF findings, and the lesions on the cranial MRI improved remarkably. This is the first case report describing the lesions on both ADCI and DWI in a case of CNS lupus. The findings of ADCI and DWI suggest that the lesions of high signal intensity on ADCI indicate interstitial edema caused by inflammatory microangiopathy, and the lesions of high signal intensity on DWI and low signal intensity on ADCI indicate cytotoxic edema caused by ischemic change resembling microinfarction. We speculate that in addition to usual T1-WI and T2-WI, performing ADCI and DWI is useful for understanding the pathogenesis of CNS lupus lesions, and may play a significant role in the prognosis.
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PMID:[A central nervous system lupus showing peculiar findings on cranial magnetic resonance imaging (MRI)]. 1458 67

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease. In human SLE patients, as well as in mouse models of SLE, the development of disease is associated with increased levels of pro-inflammatory cytokines, such as interleukin-6 (IL-6). However, IL-6 target genes contributing to the development of disease remain to be identified. Our previous studies of one mouse model of SLE identified an interferon-inducible gene, Ifi202, as a major contributor to the disease. We now report that IL-6 induces expression of the Ifi202 gene. We found that IL-6 treatment of mouse splenocytes increased levels of Ifi202 mRNA and p202 protein. Furthermore, IL-6 treatment of NIH 3T3 cells or expression of a constitutively active form of STAT3, a known mediator of IL-6 signaling, stimulated the activity of a 202-luc-reporter through a potential STAT3 DNA-binding site (the 202-SBS) present in the 5'-regulatory region of the Ifi202 gene. Moreover, treatment of cells with IL-6 stimulated binding of the transcription factor STAT3 to an oligonucleotide containing the 202-SBS in gel-mobility shift assays and to the 5'-regulatory region of the Ifi202 gene in chromatin immunoprecipitation assays. Importantly, site-directed mutagenesis of 202-SBS or expression of a dominant negative form of STAT3 significantly reduced constitutive as well as IL-6-stimulated activity of the 202-luc-reporter. Together, our observations support the idea that IL-6 stimulates transcription of the Ifi202 gene through STAT3 activation and predict that increased levels of IL-6 in lupus contribute to up-regulation of p202.
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PMID:Interleukin-6 induces expression of Ifi202, an interferon-inducible candidate gene for lupus susceptibility. 1476 8

Interleukin-6 (IL-6) is a pleiotropic cytokine with a wide range of biological activities that plays an important role in immune regulation and inflammation. Among other actions, it induces terminal differentiation of B lymphocytes into antibody-forming cells and the differentiation of T cells into effector cells. IL-6 also has multiple potent proinflammatory effects. An association between IL-6 and lupus was demonstrated in murine models of SLE and blocking IL-6 improved lupus in all models tested. Data from several studies suggest that IL-6 plays a critical role in the B cell hyperactivity and immunopathology of human SLE, and may have a direct role in mediating tissue damage. Based on these data, we propose that blocking the effect of IL-6 in humans may improve lupus by interacting with the autoinflammatory process both systemically and locally.
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PMID:Rationale for interleukin-6 blockade in systemic lupus erythematosus. 1523 Feb 89


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