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)

In order to identify possible correlations between interleukin-6 (IL-6) and hormonal and biochemical parameters of bone metabolism, or bone density, 24 postmenopausal women were studied. Serum IL-6, estradiol, calcium, phosphorus, osteocalcin, alkaline phosphatase, the urinary secretion of calcium, phosphorus and hydroxyproline, and bone density of the lumbar spine, femur and radius were measured. No significant correlation was found between IL-6 and the biochemical parameters. A negative correlation was found between IL-6 and serum estradiol, as well as between IL-6 and bone density in 5 out of 6 sites studied. It is possible that women with high IL-6 levels, may develop lower bone mass.
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PMID:Correlation of interleukin-6 serum levels with bone density in postmenopausal women. 909 98

The effects of coffee on bone metabolism are still controversial, although several studies have suggested that caffeine and/or heavy coffee consumption is associated with a significant increase in risk of fracture, osteoporosis, and periodontal disease. Therefore, we sought to clarify the relationship between coffee consumption and bone metabolism using male Wistar rats. Forty-eight male Wistar rats were assigned to three treatment groups including a control-diet group (control, n = 16, coffee-free diet), a 0.62% coffee-diet group (low caffeine, n = 16, diet supplemented with 6.2 g/kg of the control diet), and a 1.36% coffee-diet group (high caffeine, n = 16, diet supplemented with 13.6 g/kg of the control diet), and animals were maintained on an experimental diet for 140 days. Although caffeine in serum was not detected in rats fed the control diet, low-intake coffee for 140 days led to an increase in caffeine concentration to 0.53 +/- 0.11 microg/mL and high-intake coffee led to an increase of 1.77 +/- 0.22 microg/mL. No significant differences in body weight change, serum and urinary biochemical markers of bone metabolism, and bone histomorphometry were found between the coffee-diet groups and the control-diet group, except that urinary phosphorus excretion after 140 days of both coffee diets was significantly increased compared with controls (p < 0.05). In addition, the coffee diets were not associated with differences in tumor necrosis factor-alpha and interleukin-6, which have been implicated in the pathogenesis of bone loss together with interleukin-1beta. In conclusion, the present study strongly indicates that coffee does not stimulate bone loss in rats.
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PMID:Effect of coffee consumption on bone metabolism. 1124 66

Effects of a 4-week course of recombinant human erythropoietin (rHuEpo) therapy on four circulating endothelium-derived cardiovascular risk markers were studied in 20 patients receiving maintenance hemodialysis in relation to surrogates of chronic inflammation, liver function, and arterial blood pressure. Soluble intercellular adhesion molecule-1 (sICAM-1), antigens of plasminogen activator inhibitor-1 (PAI-1:Ag) and von Willebrand factor (vWF:Ag), and soluble thrombomodulin (sTM) were determined by immunoenzymatic assays. C-reactive protein; alpha1 acid-glycoprotein; alpha1-antitrypsin; immunoglobulin M, A, and G; interleukin-6; lipoprotein(a); fibrinogen; total protein; albumin; total cholesterol; hepatitis B and C markers; liver enzymes; prothrombin time; and phosphorus were measured by routine methods. The rHuEpo treatment resulted in a 25% increase in sICAM-1 (Wilcoxon's p = 0.001), a 50% increase in PAI-1:Ag (p = 0.004), a 15% increase in sTM (p = 0.002), and did not change vWF:Ag levels. The increase in sICAM-1 concentration directly correlated with that of PAI-1:Ag (Spearman's rho = 0.483, p = 0.031). The rHuEpo-induced increases in hemoglobin, platelets, and pre-dialysis diastolic blood pressure levels did not correlate with the increments in the endothelial markers studied. In conclusion, short-term rHuEpo therapy activates vascular endothelium in patients receiving maintenance hemodialysis. This specific effect may influence cardiovascular risk.
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PMID:Effects of recombinant erythropoietin therapy on circulating endothelial markers in hemodialysis patients. 1465 47

Essential amino acids, such as L-Arginine (Arg) and L-Lysine (Lys), are involved in bone metabolism and growth. Our previous studies analyzed the effect of these amino acids on rat osteoblast cultures and in experimental animals. In this study, we evaluated the effect of L-Arg and L-Lys on cultured human osteoblasts. Primary human osteoblast cultures were divided into four groups: the Arg Group received 0.625 mg/ml per day of Arg, the Lys Group 0.587 mg/ml per day of Lys, the Arg-Lys Group received both amino acids, whereas the Control Group was sham-treated. After 7 days, the following parameters were tested in all groups: alkaline phosphatase (ALP), nitric oxide (NO), calcium (Ca), phosphorus (P), osteocalcin (OC), type I collagen (PICP), interleukin-6 (IL-6), transforming growth factor-beta 1 (TGF-beta 1) on culture supernatant, platelet derived growth factor (PDGF), insulin-like growth factor-I (IGF-I), and MTT proliferation test on cells. Arg administration significantly increased ALP, NO, PICP and IGF-I production and reduced the level of IL-6. Lys administration over the same time interval mainly affected cell proliferation, as evidenced by the MTT test and immunostaining for PDGF. The same positive effects evidenced by the single administrations of the two amino acids resulted from their simultaneous administration. However, synergism could be demonstrated only for the decrease in the level of IL-6. Arg and Lys show a positive effect on human osteoblasts, which is related partly to the production of those factors required for matrix synthesis, and partly to the direct or mediated activation of cell proliferation.
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PMID:L-arginine and L-lysine stimulation on cultured human osteoblasts. 1250 70

The development of in vitro cell culture methods has made it possible to study bone cell metabolism and growth and obtain a deeper insight into the pathophysiology of common orthopedic diseases such as osteoporosis. After analyzing the effect of two essential amino acids, L-arginine (Arg) and L-lysine (Lys), in previous in vitro and in vivo studies, the present authors investigated the administration of Arg and Lys in osteoblasts derived from human osteopenic bone. After isolation, osteoblasts were cultured in DMEM supplemented with either Arg (0.625 mg/ml/day, Arg Group) or Lys (0.587 mg/ml/day, Lys Group), or both of them (Arg-Lys Group), whereas the Control Group was sham-treated. After 7 days the following parameters were tested in all groups: MTT proliferation test, Alkaline Phosphatase (ALP), Nitric Oxide (NO), Calcium (Ca), Phosphorus (P), Osteocalcin (OC), C-Terminal Procollagen type I (PICP), Interleukin-6 (IL-6), Transforming Growth Factor-beta 1 (TGF-beta 1), Platelet Derived Growth Factor (PDGF) and Insulin-Like Growth Factor-I (IGF-I). Results were compared with those obtained from human healthy bone to verify the effect of the amino acids on osteoblasts derived from pathological tissue. In addition, a comparison was also made with the results obtained from rat osteopenic bone to assess reliability of the in vitro model. The current results support previous findings and indicate that Arg and Lys stimulation has a positive effect on osteoblast proliferation, activation and differentiation. Therefore, administration of these amino acids may be useful in clinical treatment and prevention of osteoporosis.
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PMID:Human osteopenic bone-derived osteoblasts: essential amino acids treatment effects. 1260 15

Parathyroid hormone-related protein (PTHrP) plays a central role in humoral hypercalcemia of malignancy (HHM), which is one of the most frequent paraneoplastic syndromes. PTHrP produced by the tumor acts through a common PTH/PTHrP receptor to promote bone resorption, inhibit calcium excretion from the kidney, and induce hypercalcemia. Patients with HHM often develop cachexia associated with typical symptoms such as anorexia, malaise, nausea, constipation, polyuria, polydipsia, and confusion. The etiology of the cachexia is not fully understood but is thought to be caused by hypercalcemia and various cytokines such as interleukin-6, tumor necrosis factor-alpha, leukemia inhibitory factor, and others. In this study, we investigated the role of PTHrP in hypercalcemia and cachexia in HHM by using humanized anti-PTHrP antibody. A mouse monoclonal antibody that binds to PTHrP amino acid sequence 1-34 and inhibits PTHrP function has been humanized to create a specific and potent agent for the treatment of patients with HHM. The mouse monoclonal antibody has been shown to have antihypercalcemic activity against nude mice bearing human tumors. Because a mouse antibody is highly immunogenic in human patients, the complementarity-determining regions from the mouse antibody were grafted into a human antibody. The resulting humanized antibody specifically recognizes PTHrP(1-34) and neutralizes PTHrP functions in vitro and in vivo. The humanized anti-PTHrP antibody was administered intravenously to HHM model animals bearing tumors such as LC-6 human lung carcinoma. These animals showed symptoms similar to those of patients with HHM (eg, hypercalcemia and cachexia). The humanized anti-PTHrP antibody-treated animals responded with normalization of blood ionized calcium level through an improvement of bone metabolism and calcium excretion. Moreover, the treated animals also showed an improvement in body weight, ultromotivity, metabolic alkalosis, food consumption, water intake, serum phosphorus, and renal function. Consequently, the humanized antibody-treated animals experienced complete resolution of hypercalcemia and cachexia. These results suggest that the humanized antibody would be an effective and beneficial agent for patients with HHM, and that PTHrP is a major pathogenetic factor of hypercalcemia and cachexia in patients with HHM.
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PMID:Treatment of malignancy-associated hypercalcemia and cachexia with humanized anti-parathyroid hormone-related protein antibody. 1461 38

Cardiovascular disease is the leading cause of death in patients with end-stage renal disease. Although the prevalence of traditional atherosclerotic risk factors is increased in patients with chronic kidney disease, these traditional risk factors alone do not seem to account for the increased cardiovascular mortality. It has been proposed that additional risk factors may play a role in vascular injury. Among nontraditional risk factors, chronic inflammation, oxidative stress, and vascular calcification have been implicated in the accelerated athersclerosis of chronic kidney disease. Uremia is a proinflammatory state. Elevated levels of the proinflammatory cytokine interleukin-6 and suppressed levels of the anti-inflammatory cytokine interleukin-10 are present in chronic kidney disease and have been implicated in accelerated atherosclerosis. Uremia also results in increased oxidative stress. Asymmetric dimethyl arginine and myeloperoxidase may be critical mediators of the endothelial damage that results from oxidative stress. Finally, the uremic milieu seems to promote vascular calcification. The abundance of proinflammatory cytokines, the possible deficiency in calcification inhibitory proteins and the high phosphorus that are often present in uremia contribute to vascular calcification. Smooth muscle cells in calcifying lesions undergo phenotypic changes and molecular reprogramming that are reminiscent of endochondral bone formation during embryogenesis.
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PMID:Vascular biology in uremia: insights into novel mechanisms of vascular injury. 1524 45

Dietary phosphorus (P) is essential to bone growth and turnover; however, little research has focused on the genetic mechanisms controlling P utilization. Understanding the interactions between genetics and dietary P that optimize bone integrity could provide novel interventions for osteoporosis. Thirty-six pigs from two sire lines known to differ in bone structure [heavier boned (HB) and lighter boned (LB)] were assigned to one of the three diets (P adequate, P repletion or P deficient). After 14 days, bone marrow and intact radial bones were collected. Differences between these lines in growth rate, bone integrity and gene expression within bone marrow were observed. In HB, but not LB, pigs, the P-deficient diet decreased weight gain (P<.01). For both lines, P deficiency caused a reduction in radial bone strength (P<.01), but HB P-deficient animals had greater (P<.10) bone integrity than P-deficient LB pigs. In HB, but not LB, pigs, dietary treatment affected the expression of CALCR (calcitonin receptor) (P<.05), VDR (vitamin D receptor) (P<.04) and IGFBP3 (insulin-like growth factor binding protein 3) (P<.06). There was also a trend of increased IL6 (interleukin-6), TFIIB (transcription initiation factor IIB) and SOX9 (sex determining region Y-box 9) expression with P deficiency in HB, but not LB, pigs. Both genetic backgrounds responded similarly to P deficiency with an increase in the expression of OXTR (oxytocin receptor) and IGF1 (insulin-like growth factor 1). Differences in growth rate, bone integrity and gene expression within the bone marrow suggest a difference in the homeorhetic control of P utilization between these genetic lines. Understanding these differences could lead to novel treatments for osteoporosis and aid in the development of tests for identifying those at risk for this disease.
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PMID:Genetic background influences metabolic response to dietary phosphorus restriction. 1631 Oct 27

The risk of cardiovascular mortality is significantly heightened in chronic dialysis patients. Aortic wall stiffness, as reflected by aortic pulse-wave velocity (PWV), is a strong predictor of cardiovascular events. Loss of the aortic wall's elasticity is accelerated in dialysis patients because of calcifying medial arteriosclerosis, an active cellular process, controlled by calcification inducers and inhibitors. A pivotal role in the inhibition of calcium x phosphorus (Ca x P) precipitation is played by fetuin-A, a circulating plasma glycoprotein. In hemodialysis patients, lower fetuin-A concentrations were associated with increases in both cardiovascular and overall mortality. In our own study, a significant negative correlation was established between fetuin-A level and aortic PWV in chronic hemodialysis patients. The arterial-stiffening process was unaffected by the Ca x P product, but occurred independent of elevated interleukin-6 levels.
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PMID:Relationship between fetuin-A concentration, elevated levels of inflammatory markers, and arterial wall stiffness in end-stage kidney disease. 1808 50

Although cardiovascular disease is a principal cause of death in patients with chronic kidney disease (CKD), it is often asymptomatic in diabetic patients. The coronary artery calcification score (CACS) measured by multidetector computed tomography (MDCT) is useful for screening ischemic heart disease in the general population. We investigated which clinical parameters predict high CACS in predialysis diabetic nephropathy (DN). Participants were 85 patients with DN. Nobody had any history of coronary angioplasty or coronary bypass surgery. We measured blood counts, blood chemistry, bone alkaline phosphatase, intact-PTH, interleukin-6, osteoprotegerin (OPG), hemoglobin A1c, 25-hydroxyvitamin D (25(OH)D) and fetuin-A. CACS and bone mineral density (BMD) were measured by a single 16-slice MDCT and DEXA, respectively. The median value of CACS equaled 256 Agatston units (range 0-4494 units). Stepwise increase in CACS with CKD stage progression was observed (p<0.01 for trend). Simple regression analyses showed that Log (CACS+1) was positively correlated with age, systolic blood pressure, phosphorus and OPG. In addition, it was negatively correlated with nutritional parameters, such as body mass index, albumin, total-cholesterol and 25(OH)D. Fetuin-A and BMD had no impact on CACS. Multiple regression analyses showed that low albumin and high OPG were associated with high CACS. The sensitivity of OPG for detecting CACS>200 was 80%, when the cut-off value was 1.2 ng/mL. In conclusion, CACS increased with CKD stage progression in predialysis DN patients. Serum OPG was positively associated with high CACS and can be a useful screening tool for severe coronary calcification, whereas no association between fetuin-A and CACS was found.
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PMID:Serum osteoprotegerin as a screening tool for coronary artery calcification score in diabetic pre-dialysis patients. 1871 64


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