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)

Gram-negative sepsis with release of endotoxin is a frequent cause of cachexia that develops partly because of resistance to growth hormone (GH) with reduced insulin-like growth factor-I (IGF-I) expression. We set out to more fully characterize the mechanisms for the resistance and to determine whether in addition to a defect in the janus kinase 2 (JAK2)-signal transducer and activator of transcription (STAT) 5b pathway, required for GH-induced IGF-I expression, there might also be a more distal defect. Conscious rats were given endotoxin and studied 4 h later. In liver of these animals, GH-induced JAK2 and STAT5 phosphorylation was impaired and appeared to be caused, at least in part, by a marked increase in hepatic tumor necrosis factor-alpha and interleukin-6 mRNA expression accompanied by elevated levels of inhibitors of GH signaling, namely cytokine-inducible suppressors of cytokine signaling-1 and -3 and cytokine-inducible SH2 protein (CIS). Nuclear phosphorylated STAT5b levels were significantly depressed to 61% of the control values and represent a potential cause of the reduced GH-induced IGF-I expression. In addition, binding of phosphorylated STAT5b to DNA was reduced to an even greater extent and averaged 17% of the normal control value. This provides a further explanation for the impaired IGF-I gene transcription. Interestingly, when endotoxin-treated rats were treated with GH, there was a marked increase in proinflammatory cytokine gene expression in the liver. If such a response were to occur in humans, this might provide a partial explanation for the adverse effect of GH treatment reported in critically ill patients.
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PMID:Endotoxin attenuates growth hormone-induced hepatic insulin-like growth factor I expression by inhibiting JAK2/STAT5 signal transduction and STAT5b DNA binding. 1732 69

Severe or chronic disease can lead to cachexia which involves weight loss and muscle wasting. Cancer cachexia contributes significantly to disease morbidity and mortality. Multiple studies have shown that the metabolic changes that occur with cancer cachexia are unique compared to that of starvation. Specifically, cancer patients seem to lose a larger proportion of skeletal muscle mass. There are three pathways that contribute to muscle protein degradation: the lysosomal system, cytosolic proteases and the ubiquitin (Ub)-proteasome pathway. The Ub-proteasome pathway seems to account for the majority of skeletal muscle degradation in cancer cachexia and is stimulated by several cytokines including tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, interferon-gamma and proteolysis-inducing factor. Cachexia is particularly severe in pancreatic cancer and contributes significantly to the quality of life and mortality of these patients. Several factors contribute to weight loss in these patients, including alimentary obstruction, pain, depression, side effects of therapy and a high catabolic state. Although no single agent has proven to halt cachexia in these patients there has been some progress in the areas of nutrition with supplementation and pharmacological agents such as megesterol acetate, steroids and experimental trials targeting cytokines that stimulate the Ub-proteasome pathway.
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PMID:Mechanisms of skeletal muscle degradation and its therapy in cancer cachexia. 1745 54

Cachexia is common in end-stage renal disease (ESRD) patients, and it is an important risk factor for poor quality of life and increased mortality and morbidity. Chronic inflammation is an important cause of cachexia in ESRD patients. In the present review, we examine recent evidence suggesting that adipokines or adipocytokines such as leptin, adiponectin, resistin, tumor necrosis factor alpha, interleukin-6, and interleukin-1beta may play important roles in uremic cachexia. We also review the physiology and the potential roles of gut hormones, including ghrelin, peptide YY, and cholecystokinin in ESRD. Understanding the molecular pathophysiology of these novel hormones in ESRD may lead to novel therapeutic strategies.
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PMID:Adipokines and gut hormones in end-stage renal disease. 1755 23

The Apc(Min/+) mouse has a mutation in the Apc tumor suppressor gene and develops intestinal polyps, beginning at 4 wk of age. This mouse develops cachexia by 6 mo, characterized by significant loss of muscle and fat tissue. The purpose of the present study was to determine the role of circulating interleukin-6 (IL-6) and the polyp burden for the development of cachexia in Apc(Min/+) mice. At 26 wk of age, mice exhibiting severe cachectic symptoms had a 61% decrease in gastrocnemius muscle weight, complete loss of epididymal fat, a 10-fold increase in circulating IL-6 levels, and an 89% increase in intestinal polyps compared with mildly cachectic animals. Apc(Min/+)/IL-6(-/-) mice did not lose gastrocnemius muscle mass or epididymal fat pad mass while overall polyp number decreased by 32% compared with Apc(Min/+) mice. Plasmid-based IL-6 overexpression in Apc(Min/+)/IL-6(-/-) mice led to a decrease in gastrocnemius muscle mass and epididymal fat pad mass and increased intestinal polyp burden. IL-6 overexpression did not induce cachexia in non-tumor-bearing mice. These data demonstrate that IL-6 is necessary for the onset of adipose and skeletal muscle wasting in the Apc(Min/+) mouse and that circulating IL-6 can regulate Apc(Min/+) mouse tumor burden.
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PMID:Interleukin-6 and cachexia in ApcMin/+ mice. 1805 81

Rheumatoid arthritis (RA) is a chronic joint disease of undetermined cause that is associated with significant disability. Low-grade fever, anemia, and weight loss are recognized extra-articular features associated with increased disease activity. Weight loss and cachexia are well-established features of RA. The mechanism behind weight loss in RA is not known and may be multifactorial. Reduced energy intake and hypermetabolism are the major two factors frequently implicated in the etiology of RA cachexia. One would expect the effect of the above two factors to be highest during increased disease activity and lowest during remission. The purpose of this study was: (a) to establish whether in RA patients changes in body composition mirror changes in disease activity, (b) to investigate the relation between the energy expenditures and weight loss, (c) to examine the dietary energy intake and its role in weight loss in RA patients, and (d) to investigate the relation between the cytokine interleukin (IL)-6 and other variables including resting energy expenditure (REE), body composition, and acute phase reactants. Fourteen patients with RA were age-, sex-, and race-matched with 14 controls from patients with noninflammatory diseases/soft tissue rheumatism. The measurements included the following: disease activity assessment, anthropometric measurements, indirect calorimetry, and measurements of dietary intake. Blood was collected to measure the acute-phase reactants and IL-6 levels. We demonstrated that loss of fat-free mass (FFM) might accelerate during times of increased disease activity and is only partially restored during periods of reduced disease activity. This probably means that the extent of cachexia in RA patients is determined by the frequency and intensity of disease activity (flare) for a given disease duration. Hypermetabolism with increased REE was more evident during increased disease activity. Hypermetabolism in the face of increased energy intake continued to cause loss of the FFM. Interleukin-6 correlates with increased REE and erythrocyte sedimentation rate. There was no direct association between IL-6 level and low FFM. We conclude that loss of FFM is common in RA, cytokine production in RA is associated with altered energy metabolism, and preservation of FFM is important in maintaining good quality of life in patients with RA.
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PMID:The effect of disease activity on fat-free mass and resting energy expenditure in patients with rheumatoid arthritis versus noninflammatory arthropathies/soft tissue rheumatism. 1808 98

In neoplasic cachexia, chemical mediators seem to act as initiators or perpetuators of this process. Walker 256 cells, whose metabolic properties have so far been little studied with respect to cancer cachexia, are used as a model for the study of this syndrome. The main objective of this research was to pinpoint the substances secreted by these cells that may contribute to the progression of the cachectic state. Since inflammatory mediators seem to be involved in the manifestation of this syndrome, the in vitro production of nitric oxide (NO), cytokines (tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6)), and prostaglandin E2 (PGE2) was evaluated in Walker 256 cells isolated from ascitic tumors. After 4 or 5 h, a significant increase in NO production was observed (2.55 +/- 1.56 and 4.05 +/- 1.99 nmol NO per 10(7) cells, respectively). When isolated from a 6-day-old tumor, a significantly lower production of IL-6 and higher production of TNF-alpha than in cells from a 4-day-old tumor were observed, indicating a relationship between the production of cytokines and the time of tumor development after implantation. Considerable production of PGE(2) by Walker 256 cells isolated from the 6-day-old tumor was also observed. Polyamines were also determined in Walker 256 cells. Levels of putrescine, spermidine, and spermine did not show significant differences in tumors developed during 4 or 6 days. Direct evidence of the release of proinflammatory cytokines and PGE2 by Walker 256 cells suggests that these mediators can drive the cachectic syndrome in the host, the effect being dependent on tumor development time.
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PMID:Production of cachexia mediators by Walker 256 cells from ascitic tumors. 1864 74

Interleukin-6 (IL-6) is necessary for cachexia in Apc ( Min/+ ) mice, but the mechanisms inducing this myofiber wasting have not been established. The purpose of this study was to examine gastrocnemius muscle wasting in the Apc ( Min/+ ) mouse and to determine IL-6 regulated mechanisms contributing to muscle loss. Gastrocnemius type IIB mean fiber cross-sectional area (CSA) from Apc ( Min/+ ) mice decreased 32% between 13 and 22 weeks of age. Apc ( Min/+ ) mice lacking IL-6 did not have type IIB fiber atrophy, while overexpression of circulating IL-6 exacerbated the loss of type IIB fiber CSA in Apc ( Min/+ ) mice. Muscle Atrogin-I mRNA expression was induced at least ninefold at 18 and 22 weeks of age compared to 13-week-old mice. Atrogin-I gene expression was also induced by overexpression of circulating IL-6. These data suggest that high circulating IL-6 levels induce type IIB fiber CSA loss in Apc ( Min/+ ) mice, and circulating IL-6 is sufficient to regulate Atrogin-I gene expression in cachectic mice.
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PMID:Muscle wasting and interleukin-6-induced atrogin-I expression in the cachectic Apc ( Min/+ ) mouse. 1871 12

We determined the therapeutic efficacy of atractylenolide I (ATR), extracted from largehead atractylodes rhizome, in managing gastric cancer cachexia (GCC), and interpreted its probable pharmacological mechanism via investigating tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6) and proteolysis-inducing factor (PIF). This was a randomized but not-blinded pilot. The study group (n = 11) received 1.32 g per day of atractylenolide I (ATR) and the control group (n = 11) received 3.6 g per day of fish-oil-enriched nutritional supplementation (FOE) for 7 weeks. Conservative therapy was similar in both groups. Clinical [appetite, body weight, mid-arm muscle circumference (MAMC), Karnofsky performance status (KPS) status], biomarker (TNF-alpha, IL-1, IL-6 and PIF) were evaluated in the basal state, at the third and seventh weeks. To analyze changes of cytokines, an immumohistochemistry technique was adopted. Base line characteristics were similar in both groups. Effects on MAMC and body weight increase, TNF-alpha increase and IL-1 decreases of serum level were significant in both groups (P < 0.05). ATR was significantly more effective than FOE in improving appetite and KPS status, and decreasing PIF positive rate (P < 0.05). Slight nausea (3/11) and dry mouth (1/11) were shown in intervention groups but did not interrupt treatment. These preliminary findings suggest that ATR might be beneficial in alleviating symptoms, in modulating cytokine and in inhibiting PIF proteolysis of gastric cancer cachexia. Further research using a randomized controlled design is necessary to confirm these pilot study findings.
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PMID:A randomized pilot study of atractylenolide I on gastric cancer cachexia patients. 1883 Apr 51

Aging is associated with inflammatory chronic conditions such as obesity, cardiovascular disease, insulin resistance, and arthritis. Sarcopenia-muscle loss with aging-is multifactorial with contributing factors that may include loss of alpha-motor neuron input, changes in anabolic hormones, decreased intake of dietary protein, and decline in physical activity. Research findings suggest that sarcopenia is a smoldering inflammatory state driven by cytokines and oxidative stress. Elevated levels of interleukin-6 and C-reactive protein are often detected. Sarcopenic obesity manifests the added inflammatory burden of adiposity and associated adipokines. Potential interventions for sarcopenia include nutritional supplements, physical activity/resistance exercise, caloric restriction, anabolic hormones, anti-inflammatory agents, and antioxidants. A key question is whether sarcopenia is truly a distinct syndrome or a milder form of a cachexia continuum.
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PMID:Inflammation: roles in aging and sarcopenia. 1897 48

Ghrelin is an important orexigenic hormone that reduces fat oxidation and increases adiposity. This study investigated plasma ghrelin levels in Chinese Uygur patients with chronic obstructive pulmonary disease (COPD). Plasma ghrelin and anabolic and catabolic factors were measured in 38 patients and 24 control subjects. COPD patients were divided into two groups based on body mass index (BMI): underweight (BMI < 20 kg/m(2), n = 18) or normoweight (BMI > or = 20 kg/m(2), n = 20). Plasma ghrelin levels were found to be significantly higher in underweight than in normoweight patients or healthy controls. Circulating tumour necrosis factor-alpha and interleukin-6 concentrations were significantly higher in underweight than in normoweight patients, whereas insulin concentrations were significantly lower. Plasma ghrelin levels correlated negatively with forced expiratory volume in 1 s (FEV(1); r = 0.35), but did not significantly correlate with FEV(1)/forced vital capacity. Plasma ghrelin levels were elevated in underweight COPD patients and were associated with cachexia and abnormal pulmonary function.
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PMID:Plasma ghrelin levels and weight loss in Chinese Uygur patients with chronic obstructive pulmonary disease. 1909 48


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