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)

Recently in Japan, one form of vitamin B12, methylcobalamin also known as methyl B12, has attracted the attention of physicians as a therapy for patients with rheumatoid arthritis. However, its immunological actions in vivo are still unknown. In this study, we induced the in vitro production of such cytokines as interleukin-6 (IL-6), interferon-gamma (IFN-gamma), and interleukin-1 beta (IL-1 beta) by adding various mitogens (phytohemagglutinin:PHA, concanavalin A: ConA, or pokeweed mitogen:PWM) as well as recombinant interleukin-2, and we investigated the effects of methyl B12 (final concentration, 8-8,000 ng/ml) on the production of these cytokines by peripheral mononuclear cells. As compared to the controls, IL-6 production induced by PHA and ConA on Day 4 of the culture was suppressed by an average 60-70% when methyl B12 (80-8,000 ng/ml) was added to the medium. IFN-gamma production decreased dose-dependently with methyl B12, i.e., it decreased to 46% of the control when this production was induced by rIL-2, and decreased to 56-66% when it was induced by mitogens. The effect of methyl B12 on IL-1 beta production on Day I of the culture was small. These findings indicate that methyl B12 suppresses mainly the cytokine production of T lymphocytes. Such suppressive effects as shown in the in vitro situation are expected to be expressed also in vivo in patients with rheumatoid arthritis, especially at articulation lesion sites.
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PMID:Effects of methylcobalamin (vitamin B12) on in vitro cytokine production of peripheral blood mononuclear cells. 133 17

Transcobalamin (TCII) and haptocorrins (TCI and III), tumour necrosis factor alpha (TNF), interleukin-6 (IL6) and parameters of disease activity were assessed in 20 rheumatoid arthritis (RA) patients without anaemia and 19 subjects with anaemia of chronic disease (ACD) in order to determine if there was a possible correlation between these parameters. TCII, TNF and IL6 correlated positively with RA disease activity parameters, whereas their serum levels were higher in the ACD patients. TC levels were not correlated with cytokine levels. Vitamin B12 serum levels were lower in ACD. We conclude that in RA, elevated serum TCII levels are possibly mediated by increased RA disease activity, but probably not by actions of TNF or IL6. Increased TCII levels found in ACD may be explained by the higher degree of RA activity in these patients, and could also be viewed as a compensatory reaction to anaemia or reduced vitamin B12 levels. However, these preliminary findings require further confirmation.
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PMID:Elevated serum transcobalamin levels in anaemia of rheumatoid arthritis: correlation with disease activity but not with serum tumour necrosis factor alpha and interleukin 6. 160 92

Erythropoiesis is controlled by different regulators. Interleukin 3, granulocyte-macrophage colony-stimulating factor and stem cell factor play regulatory functions in the early steps of erythropoiesis. Erythropoietin (Epo) is the main factor which acts positively on the last steps of the production of erythrocytes in mammals. Epo is specific for the erythroid progenitor cells and has only little effect on other cells. The target cells for Epo are the erythroid progenitors (BFUe and CFUe). Epo acts on these progenitors through surface receptors specific for Epo. Epo induces the proliferation and differentiation of erythroid progenitors leading finally to reticulocytes. During this process, certain conditions are required to permit this differentiation: progenitors must be present in sufficient numbers, the bone marrow environment must be normal, and nutrients such as folic acid, vitamin B12 and particularly iron must be available. Elemental iron is an absolute requirement for adequate haemoglobin formation. Indeed, in a normal adult, without any stimulation, the bone marrow synthesizes 4 x 10(14) molecules of haemoglobin per second, each molecule containing four atoms of iron, which roughly corresponds to 20 mg iron. On the other hand, erythropoiesis is negatively regulated by several cytokines. These are macrophage-derived cytokines, including tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta). All these factors are elevated in the inflammatory state and are implicated in the pathogenesis of anaemia of chronic disease. TNF-alpha has an inhibitory effect on erythroid progenitors either directly or mediated by interferon-beta (INF-beta). IL-1 inhibits erythropoiesis in vivo in mice and in vitro in humans.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cellular mechanism of resistance to erythropoietin. 852 90

Periradicular tissue samples were recovered from patients undergoing endodontic surgery. Immunohistochemical procedures were used to identify interleukin-6 (IL-6) present in the neutrophils associated with these lesions. Using specific polyclonal antibody, 15 to 20% of the neutrophils associated with the periradicular tissue lesions were positive for IL-6. IL-6-positive plasma cells and histiocytes were also abundant. Cytokine production by neutrophils from the peripheral blood of nondiseased individuals was also evaluated. The cells were stimulated with lipopolysaccharides and bacterial extracts of Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. Significant levels of IL-6 were produced by cells stimulated with Escherichia coli lipopolysaccharide B5 (933 pg/ml/10(7) neutrophils) and E. coli lipopolysaccharide B12 (791 pg/ml/10(7) neutrophils) when compared with unstimulated cells (39.31 pg/ml/10(7) cells). There was a dose-dependent increase in IL-6 production when cells were stimulated for 24 h with 6 and 12 micrograms/ml of A. actinomycetemcomitans extract. Less stimulation occurred with P. gingivalis, but it was also dose-dependent. Neutrophils resident in periradicular lesions may, therefore, provide a source of IL-6 in addition to that produced by tissue histiocytes and plasma cells.
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PMID:Interleukin-6 in neutrophils from peripheral blood and inflammatory periradicular tissues. 969 75

GH deficiency is associated with increased cardiovascular mortality and early manifestations of atherosclerosis. Elevated serum homocyst(e)ine levels have been found to be associated with increased cardiovascular risk. The effect of GH replacement on homocyst(e)ine has not been investigated to date. We evaluated the effect of GH replacement on fasting homocyst(e)inemia in a group of men with adult-onset GH deficiency in a randomized, single blind, placebo-controlled trial. Forty men with adult-onset GH deficiency were randomized to GH or placebo for 18 months, with dose adjustments made according to serum insulin-like growth factor I (IGF-I) levels. Fasting serum homocyst(e)ine, folate, vitamin B12, and total T(3) levels were determined at baseline and 6 and 18 months. Anthropometry, IGF-I levels, insulin, and glucose were measured at 1, 3, 6, 12, and 18 months. Nutritional assessment, body composition, total T(4), thyroid hormone binding index, and free T(4) index were assessed every 6 months. Homocyst(e)ine decreased in the GH-treated group compared with that in the placebo group (net difference, -1.2 +/- 0.6 micromol/L; confidence interval, -2.4, -0.02 micromol/L; P = 0.047). Homocyst(e)ine at baseline was negatively correlated with plasma levels of folate (r = -0.41; P = 0.0087). Total T(3) increased in the GH-treated group vs. that in the placebo group (net difference, 0.17 +/- 0.046 ng/dL; confidence interval, 0.071, 0.26 nmol/L; P = 0.0012). Folate and vitamin B12 levels did not significantly change between groups. Changes in homocyst(e)ine were negatively correlated with changes in IGF-I. For each 1 nmol/L increase in IGF-I, homocyst(e)ine decreased by 0.04 +/- 0.02 micromol/L (P = 0.029). In contrast, changes in homocyst(e)ine did not correlate with changes in folate, vitamin B12, total T(3), C-reactive protein, interleukin-6, or insulin levels. This study shows that GH replacement decreases fasting homocyst(e)ine levels compared with placebo. This may be one of the mechanisms involved in the putative modulation of atherosclerosis and cardiovascular risk by GH replacement.
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PMID:Effects of growth hormone (GH) administration on homocyst(e)ine levels in men with GH deficiency: a randomized controlled trial. 1129 77

Hyperhomocysteinemia is an independent risk factor for atherosclerotic disease. Because serum markers of inflammation and the metabolic syndrome are also associated with atherosclerotic disease and insulin resistance, we investigated whether plasma homocysteine (Hcy) levels were associated with serum markers of inflammation and factors of metabolic syndrome in 223 elderly patients with type 2 diabetes mellitus. The levels of plasma Hcy and serum interleukin-6 (IL-6), high-sensitivity C-reactive protein, and C-peptide were measured. The C677T mutation of methylenetetrahydrofolate reductase (MTHFR) gene was detected using the polymerase chain reaction-restriction fragment length polymorphism method. The number of abnormal metabolic factors (presence of diabetes, blood pressure > or =130/85 mm Hg, triglycerides > or =150 mg/dL, high-density lipoprotein cholesterol <35 mg/dL (men) or <39 mg/dL (women), or body mass index >25 kg/m 2 ) was assessed. Elevated plasma Hcy levels correlated significantly with serum IL-6 ( r = 0.25, P < .001), C-peptide ( r = 0.22, P < .01), and the number of abnormal metabolic factors ( r = 0.20, P < .01), but not with C-reactive protein. Multiple linear regression analysis revealed that log-transformed IL-6, serum C-peptide, vitamin B12 , and creatinine were significant determinants of plasma Hcy levels. The correlation between Hcy and IL-6 levels was strongest in those with TT genotype of C677T MTHFR among 3 genotypes. The association between plasma Hcy and serum IL-6 levels supports the hypothesis that the activation of innate immunity is involved in the pathogenesis of arteriosclerosis in patients with diabetes mellitus who are homozygous for the TT genotype of C677T MTHFR.
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PMID:Association of plasma homocysteine with serum interleukin-6 and C-peptide levels in patients with type 2 diabetes. 1593 19

Rheumatoid Arthritis (RA) is a chronic inflammatory disease resulting in diarthrodial joints inflammation (particularly joints of hands, wrists, feet, knees, cubitus, ankles, shoulder, etc.) that is manifested by swelling and functional impairment. The associated complications, osteoporosis and cardiovascular disease, make RA important in public health terms. During the active phase of disease, elevated plasma concentrations of inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and acute-phase proteins, lead to reduction of fat free body mass (FFM) with a loss mean of 15% of cell body mass (CM) and consequent reduction of muscle strength. The pharmacological therapy (non steroidal anti inflammatory drugs (NSAIDs), slow acting antirheumatic drugs and corticosteroids), have the potential to cause side-effects, such as gastrointestinal bleeding, bone loss beyond to increase the requirement of some nutrients and reduce their absorption. The diet may play role in the management of RA, particularly in alleviating the symptoms of the disease, combating the side-effects of therapy and reducing the risk of complications. The increase of the caloric and proteic intake is not sufficient to offset a increased metabolic rhythm and important proteic catabolism but a diet balanced may warrant an adequate intake of nutrients. The carbohydrates of the diet provide 55-60% of the caloric intake, the diet is normo-proteinic or hyper-proteinic in the active phase of disease, and lipids represent 25-30% of the caloric intake (saturated, monounsaturated, polyunsaturated fatty acids in the ratio 1:1:1). omega-3 fatty acids supplementation, in combination with reduction of fatty acids omega-6 and adequate intake of monounsaturated fatty acids induce improvement in symptoms and sometimes a reduction in NSAIDs usage. Proper antioxidant nutrients (Vitamin A, Vitamin C, selenium) may provide an important defence against the increased oxidant stress and a supplementation of folate and vitamin B12, in patients treated with methotrexate (MTX), reduce the incidence of side effects and offset the elevation in plasma homocysteine frequent in these patients. Calcium and vitamin D, in patients treated with corticosteroids, reduce the bone loss, while a supplementation with iron may prevent anaemia. Finally, elimination diets may be feasible therapy only in patients with positive skin prick test.
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PMID:[Diet, nutrition and rheumatoid arthritis]. 1604 32

Little is known about the effects of commonly used vitamins on serum inflammatory markers and the hormonal balance in obese postmenopausal women. We studied the effects of an 8-week open-label supplementation with vitamins C (500 mg), B6 (25 mg), B12 (1 mg), and folate (5 mg) on C-reactive protein, interleukin-6, and estradiol levels in 20 obese (body mass index > or = 30) postmenopausal women. Outcomes were assessed in a blinded fashion. Folate and vitamin B12 levels rose significantly, suggesting that the supplement was well absorbed and that participants adhered to the protocol. Weight, blood pressure, and serum lipids remained stable. C-reactive protein, interleukin-6, and leptin levels remained unchanged. Estradiol levels rose from a median of 22.0 pg/mL (IQR = 15.9-25.8) at baseline to a median of 27.8 pg/mL (IQR = 23.1-33.9) at follow-up (p = 0.003). Increments in serum estradiol caused by vitamin supplementation in postmenopausal women have not been previously described and probably merit further investigation.
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PMID:Effects of short-term supplementation with ascorbate, folate, and vitamins B6 and B12 on inflammatory factors and estrogen levels in obese postmenopausal women. 1671 55

Genetics, oxidative stress: superoxide anion (O2*-) and hydrogen peroxide (H2O2), endothelial nitric oxide (eNO), lipid peroxides, anti-oxidants, endothelin, angiotensin converting enzyme (ACE) activity, angiotensinII, transforming growth factor-beta (TGF-beta), insulin, homocysteine, asymmetrical dimethyl arginine, proinflammatory cytokines: interleukin-6 (IL-6), tumor necrosis factor-a (TNF-alpha), C-reactive protein (hs-CRP), and long-chain polyunsaturated fatty acids (LCPUFAs), and activity of NAD(P)H oxidase have a role in human essential hypertension. There is a close interaction between endogenous molecules: eNO, endothelin, cytokines, and nutrients: folic acid, L-arginine, tetrahydrobiopterin (H4B), vitamin B6, vitamin B12, vitamin C, and LCPUFAs. Statins mediate some, if not all, of their actions through LCPUFAs, whereas these fatty acids (especially omega-3 fatty acids) suppress cyclo-oxygenase activity and the synthesis of pro-inflammatory cytokines, and activate parasympathetic nervous system, actions that reduce the risk of major vascular events. Some LCPUFAs form precursors to lipoxins and resolvins that have anti-inflammatory actions. Low-grade systemic inflammation seen in hypertension seems to have its origins in the perinatal period and availability of adequate amounts of LCPUFAs during the critical periods of brain growth prevents the development of hypertension. This indicates that preventive strategies aimed at decreasing the incidence of hypertension and its associated conditions such as atherosclerosis, type 2 diabetes, coronary heart disease (CHD), and cardiac failure in adulthood need to be instituted during the perinatal period if they are to be effective.
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PMID:Hypertension as a low-grade systemic inflammatory condition that has its origins in the perinatal period. 1671 19

Epidemiological studies report that a third of the cases of anaemia in older persons is unexplained. We compared erythropoietin (EPO), inflammatory markers and major comorbidities between older subjects with normal haemoglobin levels and those with different aetiologic forms of anaemia, including unexplained anaemia. Participants were a representative sample of 964 persons aged > or =65 years, with no evidence of bleeding, complete blood tests, and a complete blood count within 6 h of phlebotomy. Anaemia was defined as haemoglobin <130 g/l in men and 120 g/l in women, and classified as a result of chronic kidney disease, iron deficiency, chronic disease and B12/folate deficiency anaemia, or unexplained anaemia based on standard criteria. Of the 124 anaemic participants, 42 (36.8%) had unexplained anaemia. Participants with anaemia of chronic diseases had significantly higher interleukin-6 (IL-6) and C-reactive protein (CRP) levels, while those with unexplained anaemia had significantly lower CRP than non-anaemic controls. Iron deficiency anaemia was characterised by significantly higher EPO levels compared with other types of anaemia and normal haemoglobin, B12 and/or folate deficiency. Unexplained anaemia was characterised by unexpectedly low EPO and low lymphocyte count. Unexplained anaemia is associated with reduced kidney EPO response, low levels of pro-inflammatory markers and low lymphocyte counts.
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PMID:Unexplained anaemia in older persons is characterised by low erythropoietin and low levels of pro-inflammatory markers. 1734 Dec 72


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