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)

Interleukin-6 (IL-6) immunoreactivity has previously been shown in plaques in Alzheimer's disease (AD) and elevated IL-6 concentrations have been measured biochemically in brains of AD patients. In this study, we investigated the appearance of IL-6 immunoreactivity in AD plaques according to the stage of plaque formation. Using the Bielschowsky silver-staining method, we were able to differentiate between four types of plaques described earlier: diffuse, primitive, classic and compact. While diffuse plaques represent the early stage of plaque formation, primitive and classic plaques are thought to represent later stages of plaque development. We investigated serial sections of paraffin-embedded cortices of ten clinically diagnosed and histopathologically confirmed AD patients and ten patients with no clinical history of dementia. We found plaques in the brains of both nondemented and demented persons using the silver staining method or immunohistochemistry with antibodies against the amyloid precursor protein. In the group of clinically nondemented persons, diffuse plaques were the predominant plaque type, whereas primitive plaques formed the larger portion of lesions in the group of AD brains. IL-6 could not be detected in plaques of patients without dementia. Many IL-6-positive plaques were found in six of the AD brains and to a smaller extent in the other four AD cases. In the six cases with a large number of IL-6-positive plaques, IL-6 was found in a significantly higher ratio of diffuse plaques than expected from a random distribution of IL-6 in all plaque types.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-6 is present in early stages of plaque formation and is restricted to the brains of Alzheimer's disease patients. 767 10

Interleukin-6 (IL-6) is a pro-inflammatory cytokine with a wide range of functions. Perhaps the most important physiologically is its role as a mediator of the acute phase inflammatory response. Normally, there is little measurable IL-6 in the circulation, but levels increase abruptly to nanogram amounts during an inflammatory process. During aging, it has been proposed that the tight regulation of IL-6 gene expression becomes less effective and levels are measurable even when there is no evidence for inflammation. Several investigators have identified this cytokine as being involved in the pathogenesis of various disease processes and we have suggested that certain age-associated diseases are directly related. Among these are late-life lymphoma and myeloma, osteoporosis and possibly Alzheimer's disease.
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PMID:The role of interleukin-6 in certain age-related diseases. 783 89

The present study determined whether molecules normally associated with immune signalling processes, specifically the lymphokines interleukin-1 beta, -2, -3 and -6, can be detected in the human hippocampal formation, and whether their levels are altered in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Interleukin-1 beta, -2, -3 and -6 were measured in post mortem tissues from 14 control neurologically normal subjects, 24 patients with Alzheimer's disease and 17 patients with Parkinson's disease. In order to assess the extent of the cholinergic deficit in the Alzheimer's disease brains, choline acetyltransferase activity in the hippocampal formation was first determined. In the Alzheimer's disease tissues, choline acetyltransferase activity was significantly reduced (by 58%) compared to the control hippocampi, whereas that in the Parkinson's disease hippocampi was not significantly different from control. Using radioimmunoassays with antisera specific for the respective interleukin, marked increases in the content of immunoreactive interleukin-1 beta (99%), interleukin-2 (129%) and interleukin-3 (64%) could be detected in the Alzheimer's, but not the Parkinson's disease hippocampi. Interleukin-6 levels were not significantly different in either group, compared to the control hippocampi. Since striking elevations in various interleukins were detected in the Alzheimer's disease hippocampi, the possibility that concomitant alterations in interleukin receptor sites also occurred was investigated. Using radioligand binding to hippocampal membranes, low levels of interleukin binding were measured in the control hippocampi. In the Alzheimer's tissues, significant elevations in [125I]interleukin-1 beta (by 65%) and [125I]interleukin-2 (by 69%) binding were noted. In contrast, [125I]interleukin-3 binding was not different in the Alzheimer's disease compared to the control tissues. In the hippocampal formation of Parkinson's disease brains, only [125I]interleukin-2 binding was significantly increased (by 80%). In summary, the present results indicate that there is pronounced activation of immune system function, particularly specific immune mediators such as the interleukins, in the hippocampal formation in Alzheimer's disease, and further suggest that stimulation of immune function may be an integral component of the pathological changes that occur in this disease.
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PMID:Induction of immune system mediators in the hippocampal formation in Alzheimer's and Parkinson's diseases: selective effects on specific interleukins and interleukin receptors. 783 74

It has been suggested in recent research that interleukin-1 (IL-1) and interleukin-6 (IL-6) play a role in the pathogenesis of Alzheimer's disease (AD). Production of IL-1, by lipopolysaccharide (LPS)-stimulated monocytes, and IL-6, by phytohaemagglutinin (PHA)-stimulated mononuclear cells, was assessed in patients with AD divided into two groups--mild and moderately severe--according to severity of disease, and elderly controls. No differences in IL-1 production were found among AD patients and controls. However, significant elevation in IL-6 secretion levels was observed in both the mild and moderately severe AD patients. Our results suggest that peripheral IL-6 secretion levels may be responsible for acute-phase proteins observed in the serum of AD patients.
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PMID:Elevated interleukin-6 secretion levels by mononuclear cells of Alzheimer's patients. 797 Jan 67

Clusterin is an authentic Sertoli cell secretory product initially identified in the ram and rat testis. Subsequent studies have shown that this protein is present in almost all organs and in multiple species. Its mRNA increases in the brain undergoing degeneration as a result of infection, brain injury, and other pathological conditions such as Alzheimer's disease. However, its site(s) of synthesis and modulator(s) in the brain are not known. The objectives of this study were to determine if astrocytes could synthesize and secrete clusterin in vitro and to investigate the effects of various cytokines on the secretion and the mRNA expression of clusterin in the primary cultures of astrocytes. Astrocytes were isolated from cerebral cortices of neonatal rats and enriched to a purity of greater than 95% as judged by immunocytochemical staining using antibody against glial fibrillary acidic protein (GFAP), a specific marker of astrocytes. Using immunoprecipitation techniques, we have demonstrated that astrocytes actively synthesize and secrete clusterin in vitro. Immunocytochemical staining using a monospecific antibody against clusterin showed that this protein is localized in the entire cytoplasm and the processes of astrocytes. Treatment of astrocytes with either interleukin-1 beta, or interleukin-2, induced a significant increase in the production and the mRNA levels of clusterin, whereas other cytokines including interleukin-3, interleukin-6, and interferon-gamma had no apparent effect. The results of this study suggest that clusterin may be a marker to study the immune response in the brain.
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PMID:Regulation of clusterin secretion and mRNA expression in astrocytes by cytokines. 808 21

Interleukin-6 (IL-6) is a multifunctional cytokine that is proving to be a major contributor to the acute phase inflammatory response. IL-6 expression is normally low and serum levels are usually nondetectable in the absence of inflammation. With advancing age, however, serum levels become detectable and it is proposed that this reflects an age-associated loss in the normal regulation of gene expression for this molecule. There is also speculation that IL-6 may contribute to the pathogenesis of several diseases that are common in late-life including lymphoma, osteoporosis, and Alzheimer's disease. In this report we demonstrate that plasma levels of IL-6 rise with advancing age in well-selected healthy elderly people and comparably in old rhesus monkeys. That this change reflects a primary aging process is suggested by our findings in C57BL/6 mice in which the age-associated increase in the in vitro synthesis of IL-6 is largely prevented by life span-extending dietary restriction.
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PMID:Interleukin-6 and aging: blood levels and mononuclear cell production increase with advancing age and in vitro production is modifiable by dietary restriction. 821 95

Since immunohistochemical studies indicated the presence of interleukin-6 in the cortices of patients with Alzheimer's disease, we were interested in the eventual biological effects of this cytokine on neuronal cells. We found that interleukin-6 and interleukin-1 induced metallothionein expression in a human neuronal (SH-SY5Y neuroblastoma) cell line. In contrast to metallothionein, amyloid precursor protein expression was unaffected by both cytokines. When searching in the same cell line for the expression of the classical 80-kDa interleukin-6 binding protein, which is part of the dimeric interleukin-6 receptor, we were unable to detect the respective mRNA. Our findings either indicate that the interleukin-6 receptor in these cells is expressed in extremely low levels or that interleukin-6 may act upon neuronal cells via a different, yet unknown neuronal receptor.
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PMID:Effects of interleukin-1 and interleukin-6 on metallothionein and amyloid precursor protein expression in human neuroblastoma cells. Evidence that interleukin-6 possibly acts via a receptor different from the 80-kDa interleukin-6 receptor. 839 18

Interleukin-6 (IL-6) is a multifunctional cytokine that presumably plays its major role as a mediator of several of the acute phase inflammatory responses. These include inflammatory cell and lymphocyte activation and hepatocellular stimulation of acute phase protein synthesis. IL-6 expression is normally low, and serum levels are usually non-detectable in the absence of inflammation. However, with advancing age, serum levels become detectable, and it is proposed that this reflects an age-associated loss in the normal regulation of gene expression for this molecule. The cause of this is most likely multi-factorial, but there is evidence that it relates to an age-associated loss of T cell immunoregulatory functions as well as menopausal loss of estrogen. In any event, the "inappropriate" presence of IL-6 results in many changes typical of chronic inflammation. There is also speculation that IL-6 may contribute to the pathogenesis of several diseases of late-life including lymphoma, osteoporosis, and Alzheimer's disease. In this review the biology of this important cytokine is presented and its relevance to gerontology is highlighted.
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PMID:Interleukin-6: a cytokine for gerontologists. 842 42

Interleukin-6 (IL-6) has previously been shown to participate in neurodegenerative processes including Alzheimer's disease. However, the mechanisms leading to increased IL-6 expression in the brain remain largely unknown. We have studied the effects of synthetic ceramides and sphingomyelinase as possible regulators of IL-6 gene expression in a human astrocytoma cell line. The synthetic ceramides C2- and C6-ceramide as well as the enzyme sphingomyelinase were able to induce IL-6 gene transcription and protein synthesis in a dose-dependent manner with maximal IL-6 mRNA levels being reached after 4 h of ceramide treatment. We propose that the sphingomyelin pathway is part of the signal transduction cascade leading to IL-6 gene expression in astrocytes, and that this pathway may be involved in IL-6-mediated neurodegenerative processes.
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PMID:Stimulation of the sphingomyelin pathway induces interleukin-6 gene expression in human astrocytoma cells. 855 Aug 18

The production of interleukin-2 (IL-2) and interleukin-6 (IL-6) by peripheral blood mononuclear cells (MNC) was assessed in patients with Alzheimer's disease (AD) who were subdivided into two groups--mild and moderately-severe--according to the severity of the disease, probable vascular dementia (VaD) patients and elderly control subjects. No differences in IL-2 secretion were found between mild AD patients and controls. However, there was a significant increase in IL-2 production both in the moderately-severe AD group and in the VaD group. IL-6 levels in AD patients of both groups were similar and significantly higher than those of VaD and controls. Our results suggest that increased levels of IL-2-production correlate with severity of the dementia, whereas increased levels of IL-6 production seem to be related to AD and thus may play a role in AD pathogenesis.
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PMID:IL-2 and IL-6 secretion in dementia: correlation with type and severity of disease. 858 80


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