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)

Clinical wasting is an important risk factor for mortality in uremic patients and is reported to have a prevalence of 30-60%. 'Malnutrition' is often inappropriately used to describe a group of nutritional abnormalities in uremic patients, which are characterized by anorexia, increased basal metabolic rate, loss of lean body mass, and declining levels of serum proteins. This syndrome--more accurately described as 'cachexia'--manifests as growth failure in children with uremia. Acidosis and inflammation are important causes of uremic cachexia but the underlying molecular mechanism is not well understood. Concentrations of circulating cytokines, such as leptin, tumor necrosis factor-alpha, interleukin-1, and interleukin-6, are elevated in patients with end-stage renal disease and correlate with the degree of cachexia in these individuals. Other energy-modulating hormones such as ghrelin, and adipokines such as adiponectin and resistin, are also perturbed in uremia and could contribute to nutritional abnormalities. We recently showed that elevated levels of circulating cytokines might be an important contributor to uremia-associated cachexia via signaling through the central melanocortin system. Small-molecule melanocortin antagonists, which are biologically active when administered orally or intraperitoneally, are now available and have been used successfully to ameliorate experimental cachexia. These findings could form the basis of a novel therapeutic strategy for uremic cachexia.
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PMID:Mechanisms of disease: Cytokine and adipokine signaling in uremic cachexia. 1694 Oct 45

Body weight loss is common in cancer patients, and is often associated with poor prognosis, it greatly impairs quality of life (QOL). Radiation therapy (RT) is used in head and neck cancers (HNC) either as a primary treatment or as an adjuvant therapy to surgery. Patients with HNC are most susceptible to malnutrition especially due to anorexia, which is aggravated by RT. Multiple pro-inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1beta (IL-1beta), interferon (IFN)-gamma and tumor necrosis factor-alpha(TNF-alpha), have been all associated with the development of both anorexia and oral mucositis. Radiation-induced mucositis occurs in almost all patients, who are treated for HNC, it could also cause weight loss. Ghrelin is a novel 28-amino acid peptide, which up-regulates body weight through appetite control, increase food intake, down-regulate energy expenditure and induces adiposity. Furthermore, ghrelin inhibits pro-inflammatory cytokines such as IL-1alpha, IL-1beta, TNF-alpha which may cause oral mucositis and aneroxia, which are the results of weight loss. Thus weight loss during RT is an early indicator of nutritional decline, we propose that recombinant ghrelin used prophylactically could be useful as an appetite stimulant; and preventive of mucositis because of its anti-inflammatory effect, it might help patients maintain weight over the course of curative RT of the HNC and can improve specific aspects of QOL. This issue warrants further studies.
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PMID:Ghrelin may reduce radiation-induced mucositis and anorexia in head-neck cancer. 1882 79

The conditionally essential amino acid L-arginine is the substrate for nitric oxide (NO) synthesis, a key second messenger involved in physiological functions including endothelium-dependent vascular relaxation and inhibition of platelet adhesion and aggregation. Extracellular L-arginine transport seems to be essential for the production of NO by the action of NO synthases (NOS), even when the intracellular levels of L-arginine are available in excess (L-arginine paradox). Chronic renal failure (CRF) is a complex clinical condition associated with accelerated atherosclerosis and thrombosis leading to cardiovascular events. Various studies document that markers of malnutrition and inflammation, such as low body mass index (BMI), C-reactive protein (CRP) and interleukin-6 (IL-6), are strong independent predictors of cardiovascular mortality in patients with end-stage renal disease (ESRD). There is considerable literature demonstrating that a disturbance in the nitric oxide control mechanism plays a role in mediating the haemodynamic and haemostatic disorders present in CRF. Endogenous analogues of L-arginine, ADMA and L-NMMA, which can inhibit NO synthesis and L-arginine transport, are increased whilst L-arginine is reduced in plasma from all stages of CRF patients. In this context, the uptake of L-arginine in blood cells is increased in undialysed CRF patients and in patients treated by CAPD and haemodialysis. In platelets obtained from haemodialysis patients, the activation of L-arginine transport and NO production was limited to well-nourished patients. Impairment in nitric oxide bioactivity, coupled with malnutrition and inflammation, may contribute to increased incidence of atherothrombotic events in CRF. This article summarizes the current knowledge of L-arginine-nitric oxide pathway and malnutrition in CRF and briefly describes possible therapeutic interventions.
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PMID:Nitric oxide, malnutrition and chronic renal failure. 1743 Jan 38

Skin wound healing is mediated by inflammatory cell infiltration that is highly regulated by various adhesion molecules. Mice lacking intercellular adhesion molecule-1 (ICAM-1) delayed skin wound healing and mice lacking both L-selectin and ICAM-1 (L-selectin/ICAM-1(-/-)) show more delayed wound healing. Deficiency of both endothelial selectins (E-selectin or P-selectin) also delays wound healing. However, the relative contribution and interaction of selectins and ICAM-1 to the wound healing remain unknown. To clarify them, repair of excisional wounds was examined in L-selectin/ICAM-1(-/-) mice, wild-type mice with both E- and P-selectin blockade, and L-selectin/ICAM-1(-/-) mice with both E- and P-selectin blockade. Wild-type mice with both E- and P-selectin blockade showed delayed wound healing that was comparable with that in L-selectin/ICAM-1(-/-) mice. Combined E- and P-selectin blockade in L-selectin/ICAM-1(-/-) mice resulted in more significant delay. Mice lacking or blocked for adhesion molecules also showed suppressed keratinocyte migration, angiogenesis, granulation tissue formation, leukocyte infiltration, and cytokine expression, including transforming growth factor-beta and interleukin-6. Application of basic fibroblast growth factor (bFGF) but not platelet-derived growth factor to the wounds significantly improved wound healing in L-selectin/ICAM-1(-/-) mice with both E- and P-selectin blockade. bFGF significantly increased the leukocyte infiltration and subsequent fibrogenic cytokine production, as well as keratinocyte migration, angiogenesis, and collagen synthesis despite the loss of four kinds of adhesion molecules. These results indicate that skin wound healing is regulated cooperatively by all selectins and ICAM-1 and may provide critical information for the therapy of skin wounds.
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PMID:Endothelial selectins regulate skin wound healing in cooperation with L-selectin and ICAM-1. 1759 78

Iron balance in human beings is maintained by the control of absorption. Recent observations have demonstrated that a peptide hormone, hepcidin, is the principal regulator of iron homeostasis. It is produced in the liver in response to increasing iron stores. It is also induced by interleukin-6 (IL-6) in infectious and inflammatory diseases. Hepcidin restricts both iron absorption and iron release from stores. Disorders that affect the duodenum or stomach directly, particularly gluten enteropathy and H. pylori infections, also impair iron absorption by damaging enterocytes or reducing gastric acid output. Hepcidin secretion is suppressed by accelerated erythropoiesis even when iron stores are increased. This appears to account for the contribution that excessive absorption makes to the iron overload seen in patients with iron-loading anemias such as thalassemia major. There is some evidence suggesting that two nutritional deficiency disorders (deficiencies of vitamin A and riboflavin) lead to impaired iron absorption or utilization, but further research is needed to reconcile conflicting experimental observations.
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PMID:Influence of infection/inflammation, thalassemia and nutritional status on iron absorption. 1821 23

Chronic kidney disease (CKD) is associated with inflammation and malnutrition and carries a markedly increased risk of cardiovascular disease (CVD). High Mobility Group Box Protein-1 (HMGB-1) is a 30-kDa nuclear and cytosolic protein known as a transcription and growth factor, recently identified as a proinflammatory mediator of tissue injury. Recent data implicates HMGB-1 in endotoxin lethality, rheumatoid arthritis, and atherosclerosis. The aim of this post-hoc, cross-sectional study was to determine whether HMGB-1 serum levels are elevated in CKD patients. The study groups were categorized as follows: 110 patients starting dialysis defined as CKD 5; 67 patients with moderately to severely reduced renal function or CKD 3-4; and 48 healthy controls. High-sensitivity C-reactive-protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor (TNF), serum-albumin (S-albumin), hemoglobin A(1c) (HbA(1c)), hemoglobin, subjective global nutritional assessment (SGA), and glomerular filtration rate (GFR) were analyzed. Kruskal-Wallis test was used to compare groups and Spearman's rank correlation test was used for continuous variables. HMGB-1, measured by Western blot, was significantly (P < 0.001) elevated in CKD 5 (146.7 +/- 58.6 ng/mL) and CKD 3-4 (85.6 +/- 31.8) compared with controls (10.9 +/- 10.5). HMGB-1 levels were correlated positively with TNF (Rho = 0.52; P < 0.001), hs-CRP (Rho = 0.38; P < 0.001), IL-6 (Rho = 0.30; P < 0.001), HbA(1c) (Rho = 0.14; P = 0.02) and SGA (Rho = 0.21; P = 0.002) and negatively correlated with GFR (Rho = -0.69; P = 0.0001), Hb (Rho = -0.60; P < 0.001), S-albumin (Rho = -0.31; P < 0.001). The current study has revealed that HMGB-1 is elevated significantly in CKD patients and correlates with GFR as well as markers of inflammation and malnutrition. Future studies may delineate whether HMGB-1 is also a marker of disease activity and severity as well as a predictor of outcome in CKD.
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PMID:High Mobility Group Box Protein-1 correlates with renal function in chronic kidney disease (CKD). 1831 68

The stress and inflammatory responses to burn injury are associated with bone loss. The stress response entails production of large amounts of endogenous glucocorticoids that decrease osteoblasts on the mineralization surface of bone and decreases differentiation of marrow stromal cells into osteoblasts, thereby decreasing the amount of bone formation. Deficiency of osteoblasts also blocks osteoclastogenesis thus leading to low bone turnover and bone loss. The inflammatory response generates cytokines such as interleukin 1-beta and interleukin-6, which normally increase osteoclastogenic bone resorption via stimulation of osteoblast production of RANK ligand. However, in the absence of osteoblasts as a target we postulate that they attack the parathyroid gland chief cells and up-regulate the calcium-sensing receptor. The consequence of this upregulation is the lowering of the circulating calcium necessary to suppress parathyroid hormone production and the development of hypocalcemia and urinary calcium wasting. It is the parathyroid hormone suppression that causes us to postulate acute deficiency of 1,25-dihydroxyvitamin D and the consequence of this for post-burn metabolism could include derepression of the gene that controls renin production, leading to elevated levels of angiotensin II, which can contribute to insulin resistance, as can vitamin D deficiency itself. Moreover, the skin from burned patients cannot synthesize vitamin D normally. Thus vitamin D supplementation is the only means by which to ensure vitamin D sufficiency for burn victims. The proper requirement for vitamin D in acutely burned patients remains unknown.
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PMID:The interaction between burn injury and vitamin D metabolism and consequences for the patient. 1878 7

Intrauterine growth restriction (IUGR) is the failure of the fetus to achieve his/her intrinsic growth potential, due to anatomical and/or functional disorders and diseases in the feto-placental-maternal unit. IUGR results in significant perinatal and long-term complications, including the development of insulin resistance/metabolic syndrome in adulthood. The thrifty phenotype hypothesis holds that intrauterine malnutrition leads to an adaptive response that alters the fetal metabolic and hormonal milieu designed for intrauterine survival. This fetal programming predisposes to an increased susceptibility for chronic diseases. Although the mechanisms controlling intrauterine growth are poorly understood, adipose tissue may play an important role in linking poor fetal growth to the subsequent development of adult diseases. Adipose tissue secretes a number of hormones, called adipocytokines, important in modulating metabolism and recently involved in intrauterine growth. This review aims to summarize reported findings concerning the role of adipocytokines (leptin, adiponectin, ghrelin, tumor necrosis factor (TNF), interleukin-6 (IL6), visfatin, resistin, apelin) in early life, while attempting to speculate mechanisms through which differential regulation of adipocytokines in IUGR may influence the risk for development of chronic diseases in later life.
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PMID:Intrauterine growth restriction and adult disease: the role of adipocytokines. 1909 81

Serum transferrin, estimated by total iron-binding capacity (TIBC), may be a marker of protein-energy wasting (PEW) in maintenance hemodialysis (MHD) patients. We hypothesized that low TIBC or its fall over time is associated with poor clinical outcomes. In 807 MHD patients in a prospective 5-year cohort, associations of TIBC and its changes over time with outcomes were examined after adjustment for case-mix and markers of iron stores and malnutrition-inflammation including serum interleukin-6, iron and ferritin. Patients with serum TIBC >or=250 mg/dl had higher body mass index, triceps and biceps skinfolds and mid-arm muscle circumference and higher serum levels of iron but lower ferritin and inflammatory markers. Some SF-36 quality of life (QoL) components were worse in the lowest and/or highest TIBC groups. Mortality was incrementally higher in lower TIBC levels (p-trend <0.001). Adjusted death hazard ratio was 1.75 (95% CI: 1.00-3.05, p = 0.05) for TIBC <150 compared to TIBC of 200-250 mg/dl. A fall in TIBC >20 mg/dl over 6 months was associated with a death hazard ratio of 1.57 (95% CI: 1.04-2.36, p = 0.03) compared to the stable TIBC group. Hence, low baseline serum TIBC is associated with iron deficiency, PEW, inflammation, poor QoL and mortality, and its decline over time is independently associated with increased death risk.
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PMID:Association of serum total iron-binding capacity and its changes over time with nutritional and clinical outcomes in hemodialysis patients. 1913 18

Morbidity and mortality are markedly elevated in chronic kidney disease (CKD) patients as consequence of cardiovascular risk factors clustering. Non-traditional risk factors such as inflammation are far more prevalent in this population and contribute significantly to atherosclerosis and cardiovascular disease (CVD). CKD results in a chronic, low-grade inflammatory process that becomes evident even in the early stages of the disease. C-reactive protein (CRP) and interleukin-6 (IL-6) are the most extensively studied inflammatory biomarkers in CVD. Circulating levels of both of these factors are elevated in CKD patients and increase with renal function deterioration. In end-stage renal disease (ESRD), elevated CRP levels are a strong predictor of all-cause and cardiovascular mortality. Recent studies showed IL-6 to predict more reliably CVD and mortality in ESRD patients. However, the issue of the ideal inflammatory marker remains open. Several factors are involved in triggering the inflammatory process including patient-related factors, such as underlying disease, comorbidity, oxidative stress, infectious, genetic or immunologic factors and uremia per se, as well as those arising from dialysis treatment itself, mainly membrane and dialysate biocompatibility. This inflammatory state is associated with adverse outcomes, such as malnutrition, anemia and erythropoietin hyporesponsiveness, high rate of CVD, decreased quality of life, as well as increased mortality and hospitalization in CKD patients. There is currently no consensus on how to manage the inflammatory syndrome in this population. However, adequate knowledge of its causes and their potential prevention or treatment may improve poor clinical outcome in CKD patients.
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PMID:Inflammatory syndrome in chronic kidney disease: pathogenesis and influence on outcomes. 2002 85


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