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 cytokine interleukin-6 (IL-6) is an important mediator of inflammatory and immune responses in the periphery. IL-6 is produced in the periphery and acts systemically to induce growth and differentiation of cells in the immune and hematopoietic systems and to induce and coordinate the different elements of the acute-phase response. In addition to these peripheral actions, recent studies indicate that IL-6 is also produced within the central nervous system (CNS) and may play an important role in a variety of CNS functions such as cell-to-cell signaling, coordination of neuroimmune responses, protection of neurons from insult, as well as neuronal differentiation, growth and survival. IL-6 may also contribute to the etiology of neuropathological disorders. Elevated levels of IL-6 in the CNS are found in several neurological disorders including AIDS dementia complex, Alzheimer's disease, multiple sclerosis, systemic lupus erythematosus, CNS trauma, and viral and bacterial meningitis. Moreover, several studies have shown that chronic overexpression of IL-6 in transgenic mice can lead to significant neuroanatomical and neurophysiological changes in the CNS similar to that commonly observed in various neurological diseases. Thus, it appears that IL-6 may play a role in both physiological and pathophysiological processes in the CNS.
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PMID:Physiological and pathological roles of interleukin-6 in the central nervous system. 945 4

We investigated the levels of prolactin (PRL) and interleukin-6 (IL-6) in the cerebrospinal fluid (CSF) and serum of systemic lupus erythematosus patients with central nervous system involvement (CNS-SLE), and examined whether PRL and IL-6 have a relationship. Serum and CSF PRL and IL-6 were measured in the following groups of patients and controls: group I: seven patients with CNS-SLE; group II: three SLE patients without CNS involvement (non CNS-SLE); group III: 10 patients with neurocysticercosis; and group IV: six healthy women. The patients were clinically assessed. CSF PRL and IL-6 were elevated in group I (CNS-SLE) in comparison with all other groups (p<0.001). In addition, four of seven patients had higher levels of IL-6 and PRL in CSF than in serum. A positive correlation between PRL and IL-6 in CSF of SLE was observed (r=0.88, p<0.001). The mean serum PRL concentrations were not significantly different in all groups, but high levels of IL-6 were found in the serum of group I in comparison with groups II and IV (p<0.001). The serum levels of group III were not different from those of group I. These results demonstrate the presence of intrathecal synthesis and elevations of CSF PRL and IL-6 in active CNS-SLE involvement and indicate that measurements of CSF PRL and IL-6 may be useful in the evaluation of neuropsychiatric lupus erythematosus.
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PMID:Prolactin and interleukin-6 in neuropsychiatric lupus erythematosus. 964 6

Treatment of human peripheral blood lymphocytes (PBL) in vitro with the cytokine interleukin-6 (IL-6) induces increased levels of the 90 kDa heat shock protein (hsp90). Hsp90 levels are also elevated in PBLs of human patients with systemic lupus erythematosus (SLE) and in MRL/lpr mice with autoimmune disease. Although IL-6 is elevated in both these situations it has not been shown that it is involved in stimulating elevation of hsp90 levels in vivo. Here we show directly that the elevation of IL-6 in vivo either in mice transgenic for the IL-6 gene or in knock-out mice lacking a functional gene for the transcription factor C/EBP beta (NF-IL-6) does indeed result in elevated hsp90 levels. This overexpression is associated with the specific production of autoantibodies to hsp90 in these mice which is also observed in SLE patients and MRL/1pr mice. Hence IL-6 is likely to play a critical role in the regulation of hsp90 levels both in autoimmune disease states and potentially in normal cells in vivo. In turn the elevated levels of hsp90 produced in autoimmune diseases are likely to be responsible for the observed production of anti-hsp90 autoantibodies.
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PMID:Elevation of IL-6 in transgenic mice results in increased levels of the 90 kDa heat shock protein (hsp90) and the production of anti-hsp90 antibodies. 969 73

We report here a case of neuropsychiatric lupus erythematosus with organic brain syndrome and transverse myelitis which was successfully managed by plasmapheresis. A 27-year-old female with facial rash, arthralgia and fever was diagnosed as having SLE and treated with oral prednisolone (PSL) in June 1996. After 6 weeks she demonstrated muscle pain and a spiking temperature. The dose of PSL was increased but clinical symptoms did not improve. In August, pulse methyl-PSL was performed and she subsequently-developed delirium, impairment of orientation, memory and perception, which were followed by paraplegia of the lower extremities and loss of sphincter control. Intravenous bolus cyclophosphamide was not effective, but liver dysfunction, bone marrow suppression and respiratory failure due to an infection of pneumocystis carinii were observed. We then performed plasmapheresis or immunoabsorption several times. After this treatment steady improvement was observed. High values of antiribosomal P protein antibodies in the serum and interleukin-6 in the cerebrospinal fluid decreased. Small foci of increased signal intensity detected on cranial magnetic resonance imaging and hypoperfused areas on single-photon emission CT diminished. The patient was maintained on low-dose PSL and no recurrence has been observed 15 months from the onset.
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PMID:[A case of severe neuropsychiatric lupus erythematosus treated by plasmapheresis: diagnostic values of serum antiribosomal P protein antibodies and interleukin-6 in cerebrospinal fluid]. 979 79

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.
Lupus 1999
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

A 29-year-old woman experienced Raynaud's phenomenon, swelling of her fingers, eruptions on her face, and muscle weakness in 1990. She was diagnosed as having mixed connective tissue disease (MCTD) and was treated with prednisolone (PSL) for 3 years. Most of her complaints disappeared after the treatment. In March 1997, she experienced fever, erythema, and lymphadenopathy. Although she was treated with PSL (20 mg/day) again, muscle weakness, mental disturbance, and recto-urinary disturbance appeared. When she was re-admitted to our hospital, increased levels of muscle-derived enzymes and positivity of anti-RNP antibody were found. High signal areas in her cerebrum were shown by magnetic resonance imaging, and slow and spike pattern was shown by electroencephalography. Hypoperfusion of the cerebral blood flow was suggested on single photon emission computed tomography. The number of mononuclear cells, amount of protein and level of interleukin-6 were found to be elevated in her cerebrospinal fluid (CSF). Her neurological manifestations were diagnosed as being due to MCTD, and showed characteristics similar to those of systemic lupus erythematosus. She was treated with PSL (60 mg/day) followed by steroid pulse therapy. Because the response to this treatment was partial, oral administration of cyclophosphamide (CPM) (100 mg/day) was added. Muscle weakness and neurological abnormalities as well as abnormal laboratory findings gradually improved over the following two months. We conclude that the treatment with CPM combined with PSL may be useful, when neurological manifestations of MCTD are serious and resistant to conventional therapy.
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PMID:[A case of mixed connective tissue disease with lupus-like manifestations of the central nervous system, successfully treated with cyclophosphamide combined with prednisolone]. 1092 Jun 88

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 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.
Lupus 2001
PMID:Lipid-lowering drugs in lupus: an unexplored therapeutic intervention. 1131 59


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