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)

Tenidap is a structurally novel antirheumatic agent with anti-inflammatory and analgesic properties. Previous studies have shown that tenidap is able to inhibit the production and action of cytokines such as interleukin-1, interleukin-6 (IL-6) and tumour necrosis factor alpha. However, the mechanisms by which tenidap inhibits cytokine synthesis are not yet known. We investigated in the human astrocytoma cell line U373 whether tenidap inhibits IL-6 synthesis by inhibition of certain signal transduction processes leading to IL-6 synthesis. Cells were stimulated with different substances which have previously been shown to activate protein kinase A or C, reactive oxygen intermediates as well as transcription factors such as nuclear factor kappa B and AP-1 and which all result in IL-6 synthesis. Tenidap was a very potent inhibitor of IL-6 synthesis independent of the stimuli used, suggesting an inhibitory mechanism other than inhibition of a certain signal transduction pathway. Since IL-6 has been shown to be involved in the etiopathology of Alzheimer's disease and since the use of nonsteroidal anti-inflammatory drugs appears to be of therapeutical benefit, it is concluded that tenidap should be tested in clinical trials in order to determine whether it may be useful for the treatment of Alzheimer's disease.
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PMID:Potent inhibition of interleukin-6 expression in a human astrocytoma cell line by tenidap. 908 60

Several lines of evidence indicate an immune-mediated pathophysiology of Parkinson's disease (PD) and Alzheimer's disease (AD). In clinical studies the monoamine oxidase-B inhibitor Selegiline appears to slow the progression of neurological deficits in PD and the cognitive decline in AD. The immune response to bacterial or viral infection and in chronic inflammatory processes is stimulated by an increased synthesis of the cytokines interleukin-1 beta (IL-1 beta) and subsequently interleukin-6 (IL-6). We investigated the influence of Selegiline on the synthesis of IL-1 beta and IL-6 in peripheral blood mononuclear cells (PBMC) from healthy blood donors cultured with or without Selegiline (10(-8)M, 10(-9)M or 10(-10)M) in a humidified atmosphere (7% CO2). Treatment of cultured PBMC with Selegiline significantly increased synthesis of both cytokines. The effect of Selegiline on cytokine biosynthesis may contribute to its putative neuroprotective properties.
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PMID:Selegiline stimulates biosynthesis of cytokines interleukin-1 beta and interleukin-6. 911 94

The effects of indometacin (CAS 53-86-1) on lipopolysaccharide-induced impairment of active avoidance and on interleukin-6-induced increase of prostaglandin E2 release were investigated in rats. In the experiment on acquisition and retention of one-way active avoidance in a shuttle box model, bilateral infusion of lipopolysaccharides (LPS) into the hippocampus, 1 microgram per side, resulted in a significant impairment both in acquisition and retention by prolonging the latency of avoidance in training and testing. In the meantime, intraperitoneal injection of indometacin 10 mg/kg daily for 7 days, improved the LPS-induced amnesia especially in the testing by shortening the latency from 2.3 to 1.7 s (p < 0.05). In the in vivo microdialysis study in anesthetized rats, intrahippocampal infusion of 80 ng interleukin-6 (IL-6) markedly increased prostaglandin E2 (PGE2) release into hippocampal dialysates which started at 2 h post administration. Perfusion of indometacin (0.3 mol/l) into the hippocampus for 1 h obviously suppressed the IL-6-induced PGE2 response. These findings provide experimental evidence that--assuming that central inflammation may be involved with Alzheimer's disease a non-steroidal anti-inflammatory drug may be used in the treatment of Alzheimer's disease.
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PMID:Suppression of lipopolysaccharide-induced impairment of active avoidance and interleukin-6-induced increase of prostaglandin E2 release in rats by indometacin. 920 71

We investigated interleukin-6 (IL-6) levels in cerebrospinal fluid (CSF) of 25 patients with clinically diagnosed sporadic Alzheimer's disease (AD) and 19 healthy control subjects (HC). For comparison 19 clinically healthy subjects with at least one first-degree relative with clinical or autopsy confirmed AD (CF/AD) were examined. CSF levels of IL-6 did not show statistically significant differences between AD patients, CF/AD and HC subjects. There was no correlation between age, gender, age of onset, degree of cognitive impairment, blood-brain barrier dysfunction and IL-6 values. We could not demonstrate altered CSF concentrations of IL-6 that may indicate an inflammatory response or capability to support neuronal survival in the central nervous system (CNS) of first-degree relatives and patients with AD. We suggest that combined measurement of all parameters of the IL-6-receptor complex could yield more insight in a probably altered IL-6 function.
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PMID:Interleukin-6 is not altered in cerebrospinal fluid of first-degree relatives and patients with Alzheimer's disease. 921 28

Interleukin-6 (IL-6), a member of the neuropoietic cytokine family, initially was described in terms of its activities in the immune system and during inflammation. Accumulating evidence supports an essential role of IL-6 in the development, differentiation, regeneration and degeneration of neurons in the peripheral and central nervous system. Major sites of IL-6 synthesis are neurons and glial cells. Interleukin-6 functions are mediated by a specific receptor system composed of a binding site and a signal transducer. This receptor system can be modulated by a complex of IL-6 and soluble IL-6 receptor acting as agonist. The IL-6 can exert completely opposite actions on neurons, triggering either neuronal survival after injury or causing neuronal degeneration and cell death in disorders such as Alzheimer's disease. Development of selective IL-6 agonists and antagonists, as well as the usage of soluble IL-6 receptors, offers new possibilities for the treatment of neurodegenerative disorders. Furthermore, optimized genetic mouse models, including transgenic and knockout animals, should help to define the physiological and pathophysiological role of IL-6 in the nervous system.
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PMID:Interleukin-6 (IL-6)--a molecule with both beneficial and destructive potentials. 930 98

Immune factors may be involved in the pathophysiology of Alzheimer's disease (AD), a neurodegenerative disease. Since immune activation precedes immune-mediated processes, we measured plasma levels of four selective cytokines: interleukin-6 (IL-6), interleukin-12 (IL-12), interferon-alpha (IFN-alpha), and interferon-gamma (IFN-gamma). The level of IL-6, but not other cytokines, was significantly elevated. The increase of circulating IL-6 indicates immune activation presumably related to pathophysiology of the disease.
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PMID:Circulating cytokines in Alzheimer's disease. 944 70

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

Interleukin-6 may play an essential role in early inflammatory processes as response to degenerating cholinergic cells in the nucleus basalis of Meynert in patients suffering Alzheimer's disease. The cholinergic immunotoxin, 192IgG-saporin, was applied to produce selective and specific degenerations of basal forebrain cholinergic cells. To disclose the lesion-induced temporal cascade of the expression pattern of IL-6, and to reveal the cellular source for production and secretion of IL-6 in vivo after endogeneously induced basal forebrain cholinergic cell loss, both in situ hybridization and immunocytochemistry for IL-6 were performed. To identify the cell types expressing IL-6 mRNA, double labeling techniques were applied combining in situ hybridization technique with immunocytochemistry and lectin histochemistry for both micro- and astroglia and a number of neuronal markers including choline acetyltransferase, parvalbumin, and neurofilaments. In the intact brain, IL-6 is mainly localized in neurons, in particular in both cholinergic and GABAergic neurons of the basal forebrain. Although basal forebrain cholinergic lesion resulted in a dramatic increase in the number of micro- and astroglial cells at the lesion site, IL-6 expression could not be detected in any of the lesion-induced activated glial cell types. Moreover, cholinergic lesion led to a reduced number of IL-6-expressing cells in the basal forebrain, which is assumed to be due to the loss of cholinergic cells. The predominantly neuronal localization in rat brain suggests a role for IL-6 in activating micro- and astroglial cells in response to degenerating cholinergic neurons.
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PMID:Interleukin-6 is not expressed in activated microglia and in reactive astrocytes in response to lesion of rat basal forebrain cholinergic system as demonstrated by combined in situ hybridization and immunocytochemistry. 946 76

The function of the cytokine interleukin-6 (IL-6) is augmented by soluble IL-6 receptors (sIL-6R). We investigated cerebrospinal fluid sIL-6R concentrations in patients with Alzheimer's disease (AD) compared to age-matched healthy subjects and individuals with at least one first degree relative with AD. We found a statistically significant decrease in sIL-6R levels in the AD group compared to controls. Complete analysis of the IL-6R complex seems crucial to better understand the impact of IL-6 in AD pathophysiology.
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PMID:Decreased soluble interleukin-6 receptor in cerebrospinal fluid of patients with Alzheimer's disease. 950 94

Interleukin-6 (IL-6) is a proinflammatory cytokine whose synthesis is induced by a variety of stimuli including interleukin-1 (IL-1), substance P (SP), and histamine. Because IL-6 has been implicated in the etiopathology of different human diseases including multiple myeloma, rheumatoid arthritis, multiple sclerosis, acquired immunodeficiency syndrome dementia complex, and Alzheimer's disease, its inhibition may be of therapeutic interest. A main demand on an effective inhibitor of IL-6 expression is that it inhibits IL-6 synthesis independently of the inducing stimulus. We therefore used human astrocytoma cells to search for signal transduction cascades and transcription factors whose inhibition suppresses IL-6 synthesis after stimulation with three different inductors, IL-1beta, SP, and histamine. Whereas the antioxidant pyrrolidinedithiocarbamate was only able to inhibit IL-1beta-induced IL-6 expression, inhibition of protein kinase C prevented IL-6 expression induced by all three substances. Promoter deletion analysis revealed that IL-1beta-induced IL-6 expression required the transcription factor nuclear factor-kappaB (NF-kappaB), whereas SP- and histamine-induced IL-6 synthesis was essentially controlled by NF-IL-6. These findings suggest that inhibition of protein kinase C or a combinatory inhibition of NF-IL-6 and NF-kappaB binding are strategies to effectively suppress IL-6 synthesis. They therefore provide the basis for the development of antiinflammatory drugs used to treat disorders in which IL-6 is pathogenically involved.
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PMID:Substance P and histamine induce interleukin-6 expression in human astrocytoma cells by a mechanism involving protein kinase C and nuclear factor-IL-6. 952 75


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