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) is a multipotential cytokine which may act as a growth factor for keratinocytes. The epidermal hyperplasia of psoriasis may be explained in part by an overproduction of this cytokine. We have previously shown by in situ hybridization that IL-6 mRNA is most strongly expressed in the peripheral lesion of an advancing psoriatic plaque. In the present study, we investigated whether there were differences between the expression of IL-6 in untreated psoriatic epidermis and the lesion during the course of clinical improvement. In the untreated psoriatic lesion, the weak expression of IL-6 mRNA was localized in the lower epidermis. However, IL-6 mRNA was not detected in the clearly improved lesion. In the improving lesion, with clinically less scaling, less induration, and histologically thinner epidermis, IL-6 mRNA-expressing keratinocytes were detectable in a greater proportion of the total epidermal components than in the untreated, fully developed lesion. These results showed that IL-6 mRNA was strongly expressed in lesions with moderate epidermal hyperproliferation, indicating that this cytokine may play a role in the transitional phase during the course of improvement as well as in the lesion's formation.
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PMID:In situ expression of interleukin-6 in psoriatic epidermis during treatment. 805 14

This paper describes a study of whether or not the amounts of interleukin-6 (IL-6) in gingival crevicular fluid (GCF) are correlated with periodontal clinical measures. A sensitive ELISA was developed to measure IL-6 in GCF. Two male and 3 female adult subjects with periodontal disease were examined at their first appointments, after 3 months, and after 6 months. Data were obtained on plaque index (PI), bleeding index (BI), probing depth (PD), and on the IL-6 content of GCF samples from 16 sites per subject for a total of 240 measurements. Significant correlations were found between BI and IL-6 (P < 0.005) and between PD and IL-6 (P < 0.05), but not between PI and IL-6. Only 6 out of the 80 sites (in 3 of the 5 subjects) showed PD increases of at least 2 mm. However, for each of these 3 subjects, the amounts of IL-6 in the GCF samples from these sites were markedly higher than the mean amounts of IL-6 in the GCF samples from the remaining sites. These findings suggest that IL-6 may be a useful indicator of periodontal disease, although more extensive longitudinal studies are needed to determine the real clinical value of this GCF component.
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PMID:Measurements of interleukin-6 in gingival crevicular fluid from adults with destructive periodontal disease. 827 8

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 report, we present data on the appearance of IL-6 immunoreactivity in AD plaques according to the stage of plaque formation. Diffuse plaques are found in the early stages of plaque formation, whereas primitive and classic plaques are thought to represent later stages of plaque pathology. We classified plaques using the Bielschowsky silver stain method in serial sections of paraffin-embedded cortices of clinically diagnosed and histopathologically confirmed AD patients and patients with no clinical history of dementia. In the brains of nondemented and demented persons, we found plaques using the silver staining method or immunohistochemistry with antibodies against the amyloid precursor protein. In the nondemented group, diffuse plaques were the predominant plaque type, whereas primitive plaques formed the larger proportion of lesions in the group of AD brains. IL-6 was only detectable in plaques of demented patients. In AD cases, IL-6 was found in a significantly higher ratio in diffuse plaques as would have been expected from a random distribution of IL-6 in all plaque types. We conclude that the presence of IL-6 immunoreactivity correlates with clinically detectable dementia. In addition to the ubiquitous presence of amyloid in nondemented and demented brains, an IL-6-related immunological mechanism may be involved both in the transformation from diffuse to primitive plaques in AD and in the development of dementia.
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PMID:Occurrence of interleukin-6 in cortical plaques of Alzheimer's disease patients may precede transformation of diffuse into neuritic plaques. 862 85

In recent years many studies have indicated an involvement of inflammatory mechanisms in Alzheimer's disease (AD). Acute-phase proteins such as alpha 1-antichymotrypsin and c-reactive protein, elements of the complement system, and activated microglial and astroglial cells are consistently found in brains of AD patients. Most importantly, also cytokines such as interleukin-6 (IL-6) have been detected in the cortices of AD patients, indicating a local activation of components of the unspecific inflammatory system. Up to now it has remained unclear whether inflammatory mechanisms represent a primary event or only an unspecific reaction to brain tissue damage. Therefore, we investigated whether IL-6 immunoreactivity could be found in plaques prior to the onset of neuritic changes, or whether the presence of this cytokine is restricted to later stages of plaque pathology. We confirmed our previous observation that IL-6 is detectable in a significant proportion of plaques in the brains of demented patients. In AD patients IL-6 was found in diffuse plaques in a significant higher ratio as would have been expected from a random distribution of IL-6 among all plaque types. This observation suggests that IL-6 may precede neuritic changes, and that immunological mechanism may be involved both in the transformation from diffuse to neuritic plaques in AD and in the development of dementia.
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PMID:Inflammatory mechanisms in Alzheimer's disease. 873 96

A loss of synapses in the cortices of demented persons appears to be the primary correlate of Alzheimer's disease (AD). However, it is still unclear how synaptic pathology is connected to other pathological findings such as neurofibrillary and neuritic degeneration or inflammatory markers in AD. Interleukin-6 (IL-6) immunoreactivity has previously been detected in plaques in the brains of AD patients. In addition, elevated IL-6 concentrations have been measured biochemically in the brains of AD patients. Since transgenic mice bearing additional copies of the IL-6 gene under the control of a brain-specific promoter develop a marked cortical pathology including severe alterations of the dendritic arborization of cortical neurons, an IL-6 related inflammatory event could well be connected to the synaptic pathology in AD. In this study, we investigated whether IL-6 immunoreactivity in plaques could already be found prior to the onset of neuritic changes, or whether the presence of this cytokine is restricted to the later stages of plaque formation. While diffuse plaques represent an early stage of plaque formation, primitive and classic plaques (displaying neuritic pathology) are thought to reflect later stages of plaque pathology. Using a silver-staining method, we classified plaque stages in serial sections of paraffin-embedded cortices of clinically diagnosed and histopathologically confirmed AD patients and of control persons with no clinical history of dementia. Adjacent sections were stained with an antibody directed against IL-6. IL-6 was detectable in a significant proportion of plaques, but only in the brains of demented patients. In the AD cases, IL-6 was found in diffuse plaques in a significantly higher ratio as would have been expected from a random distribution of IL-6 among all plaque types. This observation suggests that IL-6 expression may precede neuritic changes and that in AD an immunological mechanism may be involved both in the transformation from diffuse to primitive plaques and in the development of dementia. The reasons for the increased expression of IL-6 in the brains of AD patients are still unknown. Basal IL-6 levels were found to be slightly elevated along normal aging. Based on several studies indicating that IL-6 expression is inducible also by psychological stress, one could speculate whether long-lasting stressful experiences may contribute to the pathological process underlying Alzheimer's disease.
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PMID:The participation of interleukin-6, a stress-inducible cytokine, in the pathogenesis of Alzheimer's disease. 879 35

Interleukin-6 (IL-6), among other cytokines, is thought to be involved in the regulation of sickness behavior (e.g., anorexia, cachexia, fever, and lethargy) induced by infections bacterial and viral origin) and sterile tissue necrosis (burns and surgical traumas). Mice deficient in IL-6 (IL-6 KO) were generated by gene targeting. Homozygous IL-6 KO male and female mice and their appropriate controls were implanted with biotelemeters to monitor body temperature (Tb) and motor activity (Act). Normal circadian rhythms in Tb and Act as well as rates of food intake and weight gain did not differ significantly between sex-matched IL-6 KO and control groups at 30 degrees C in a 12:12-h light-dark cycle. Sterile tissue damage was induced in mice by subcutaneous injection of turpentine (0.1 ml, left hindlimb). Influenza pneumonitis was induced by intranasal inoculation of mouse-adapted influenza A virus (17.5 plaque-forming units). Lack of IL-6 completely prevented fever, anorexia, and cachexia because of turpentine abscess in both sexes. It did not prevent lethargy, although IL-6 KO mice recovered to normal Act significantly sooner than wild-type mice. Symptoms of sickness were only slightly modified during influenza virus infection in IL-6 KO mice. Attenuation of sickness behavior was more pronounced in IL-6 KO female than in male mice. We conclude that, although IL-6 is induced during both turpentine abscess and influenza infection, this cytokine appears to be more critical in induction of the symptoms of sickness behavior during sterile tissue abscess than during influenza infection.
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PMID:Sickness behavior in mice deficient in interleukin-6 during turpentine abscess and influenza pneumonitis. 912 87

Enteric infection of mice with respiratory enteric orphan virus (reovirus) type 1, strain Lang elicits both humoral and cellular immune responses. To investigate the role of CD8+, alpha/beta T-cell receptor (TCR)+ T cells in mucosal immunity to an enteric pathogen, we examined immune responses and viral clearance following enteric reovirus infection in C57BL/6, B6129F2, and beta2-microglobulin-deficient (beta2m-/-) mice. Analysis of Peyer's patch and lamina propria culture supernatants revealed a two- to threefold increase in levels of reovirus-specific immunoglobulin A in beta2m-/- mice compared to normal controls. These data corresponded to a similar increase in the frequency of virus-specific immunoglobulin A-producing cells in Peyer's patches and lamina propria and an increase in immunoglobulin G-producing cells in spleens from beta2m-/- mice compared to controls. These increased humoral immune responses were not due to a difference in B-cell populations because cell counts and flow cytometric analyses showed that beta2m-/- and control mice had similar numbers and percentages of B cells in mucosal and systemic tissues. Analysis of cytokine message by reverse transcriptase-PCR 5 and 10 days after infection revealed no difference in message level for transforming growth factor beta, gamma interferon, interleukin-4, interleukin-5, or interleukin-6 for all mouse strains. Virus tissue titers determined by plaque assay at 5 and 10 days after infection demonstrated that beta2m-/- mice cleared reovirus from the small intestines with the same efficiency as control mice. Collectively, these data suggest that CD8+, alpha/beta TCR+ T cells may regulate mucosal and systemic humoral immune responses to oral infection with reovirus.
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PMID:Enhanced mucosal and systemic immune responses to intestinal reovirus infection in beta2-microglobulin-deficient mice. 922 66

Human hepatoma cells (HepG2) synthesize and secrete several plasma proteins that are inhibited in a time- and dose-dependent manner after vaccinia virus infection. However, infection of the HepG2 cells with a low dose of the virus (up to 1 plaque forming unit/cell) stimulated the expression of alpha-1-antichymotrypsin, which was demonstrated by means of electroimmunoassay and Northern blot analysis. This stimulation appeared to be on the level of transcription as shown in transient transfection experiments using various alpha-1-antichymotrypsin gene promoter constructs. In contrast to interleukin-6, virus-induced activation of the alpha-1-antichymotrypsin gene transcription does not require the STAT (signal transducers and activators of transcription) binding elements present in the alpha-1-antichymotrypsin gene promoter. Furthermore, alpha-amanitin, which inhibits eukaryotic RNA polymerase II and III, did not affect alpha-1-antichymotrypsin stimulation by the virus, indicating involvement of the viral transcriptional apparatus in transient activation of alpha-1-antichymotrypsin gene expression.
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PMID:Changes in alpha-1-antichymotrypsin expression in vaccinia virus infected HepG2 cells. 952 74

Peroxisome proliferator-activated receptors (PPARs) are key players in lipid and glucose metabolism and are implicated in metabolic disorders predisposing to atherosclerosis, such as dyslipidaemia and diabetes. Whereas PPARgamma promotes lipid storage by regulating adipocyte differentiation, PPARalpha stimulates the beta-oxidative degradation of fatty acids. PPARalpha-deficient mice show a prolonged response to inflammatory stimuli, suggesting that PPARalpha is also a modulator of inflammation. Hypolipidaemic fibrate drugs are PPARalpha ligands that inhibit the progressive formation of atherosclerotic lesions, which involves chronic inflammatory processes, even in the absence of their atherogenic lipoprotein-lowering effect. Here we show that PPARalpha is expressed in human aortic smooth-muscle cells, which participate in plaque formation and post-angioplasty re-stenosis. In these smooth-muscle cells, we find that PPARalpha ligands, and not PPARgamma ligands, inhibit interleukin-1-induced production of interleukin-6 and prostaglandin and expression of cyclooxygenase-2. This inhibition of cyclooxygenase-2 induction occurs transcriptionally as a result of PPARalpha repression of NF-kappaB signalling. In hyperlipidaemic patients, fenofibrate treatment decreases the plasma concentrations of interleukin-6, fibrinogen and C-reactive protein. We conclude that activators of PPARalpha inhibit the inflammatory response of aortic smooth-muscle cells and decrease the concentration of plasma acute-phase proteins, indicating that PPARalpha in the vascular wall may influence the process of atherosclerosis and re-stenosis.
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PMID:Activation of human aortic smooth-muscle cells is inhibited by PPARalpha but not by PPARgamma activators. 965 93

Increased levels of interleukin-6 (IL-6) have been proposed to contribute to a number of pathological disorders, including osteoporosis and Alzheimer's disease. In human atherosclerotic lesions, IL-6 protein and mRNA have been detected, although the role of IL-6 in plaque formation is unknown. We have examined the expression pattern of IL-6 mRNA and secreted protein in male apolipoprotein E-knockout (apoE-KO) mice aortas. Furthermore, we have evaluated the effects of 17beta-estradiol (E2), a vasculoprotective sex steroid hormone, on the secretion of this inflammatory cytokine from isolated male apoE-KO mice aortas. The expression of IL-6 mRNA was detected by reverse transcription-polymerase chain reaction in the apoE-KO mouse aortas but not in the aortas of age-matched control mice. Similarly, the secretion of IL-6 protein from isolated apoE-KO aortic segments was significantly greater than that from aortas of age-matched control animals. The secretion of IL-6 from isolated aortic rings of apoE-KO mice ranging in age from 6 to 48 weeks showed a significant, positive correlation with percent lesion area measured in the same tissue. Immunohistochemical staining of apoE-KO mouse aortic tissue sections demonstrated colocalization of IL-6 expression with macrophages. Treatment of male apoE-KO mice with E2 for 3 weeks resulted in a statistically significant 50% reduction in IL-6 secretion from ex vivo aortic tissue segments. There was no significant change in total serum cholesterol and triglyceride levels in the E2-treated group compared with placebo-treated controls. These data demonstrate that (1) IL-6 mRNA and protein are expressed in the atherosclerotic plaques of apoE-KO mice aortas and (2) IL-6 production is suppressed by E2 treatment, which may contribute to the antiatherosclerotic effects of E2 in the apoE-KO mouse model of atherosclerosis.
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PMID:Expression of interleukin-6 in atherosclerotic lesions of male ApoE-knockout mice: inhibition by 17beta-estradiol. 974 40


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