Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cachexia-anorexia syndrome occurs in chronic pathophysiologic processes including cancer, infection with human immunodeficiency virus, bacterial and parasitic diseases, inflammatory bowel disease, liver disease, obstructive pulmonary disease, cardiovascular disease, and rheumatoid arthritis. Cachexia makes an organism susceptible to secondary pathologies and can result in death. Cachexia-anorexia may result from pain, depression or anxiety, hypogeusia and hyposmia, taste and food aversions, chronic nausea, vomiting, early satiety, malfunction of the gastrointestinal system (delayed digestion, malabsorption, gastric stasis and associated delayed emptying, and/or atrophic changes of the mucosa), metabolic shifts, cytokine action, production of substances by tumor cells, and/or iatrogenic causes such as chemotherapy and radiotherapy. The cachexia-anorexia syndrome also involves metabolic and immune changes (mediated by either the pathophysiologic process, i.e., tumor, or host-derived chemical factors, e.g., peptides, neurotransmitters, cytokines, and lipid-mobilizing factors) and is associated with hypertriacylglycerolemia, lipolysis, and acceleration of protein turnover. These changes result in the loss of fat mass and body protein. Increased resting energy expenditure in weight-losing cachectic patients can occur despite the reduced dietary intake, indicating a systemic dysregulation of host metabolism. During cachexia, the organism is maintained in a constant negative energy balance. This can rarely be explained by the actual energy and substrate demands by tumors in patients with cancer. Overall, the cachectic profile is significantly different than that observed during starvation. Cachexia may result not only from anorexia and a decreased caloric intake but also from malabsorption and losses from the body (ulcers, hemorrhage, effusions). In any case, the major deficit of a cachectic organism is a negative energy balance. Cytokines are proposed to participate in the development and/or progression of cachexia-anorexia; interleukin-1, interleukin-6 (and its subfamily members such as ciliary neurotrophic factor and leukemia inhibitory factor), interferon-gamma, tumor necrosis factor-alpha, and brain-derived neurotrophic factor have been associated with various cachectic conditions. Controversy has focused on the requirement of increased cytokine concentrations in the circulation or other body fluids (e.g., cerebrospinal fluid) to demonstrate cytokine involvement in cachexia-anorexia. Cytokines, however, also act in paracrine, autocrine, and intracrine manners, activities that cannot be detected in the circulation. In fact, paracrine interactions represent a predominant cytokine mode of action within organs, including the brain. Data show that cytokines may be involved in cachectic-anorectic processes by being produced and by acting locally in specific brain regions. Brain synthesis of cytokines has been shown in peripheral models of cancer, peripheral inflammation, and during peripheral cytokine administration; these data support a role for brain cytokines as mediators of neurologic and neuropsychiatric manifestations of disease and in the brain-to-peripheral communication (e.g., through the autonomic nervous system). Brain mechanisms that merit significant attention in the cachexia-anorexia syndrome are those that result from interactions among cytokines, peptides/neuropeptides, and neurotransmitters. These interactions could result in additive, synergistic, or antagonistic activities and can involve modifications of transducing molecules and intracellular mediators. Thus, the data show that the cachexia-anorexia syndrome is multifactorial, and understanding the interactions between peripheral and brain mechanisms is pivotal to characterizing the underlying integrative pathophysiology of this disorder.
 ...
PMID:Central nervous system mechanisms contributing to the cachexia-anorexia syndrome. 1105 8

The current understanding of the origin of atherosclerosis is that of an inflammatory process that involves the acute phase response -an innate biological response to a disturbance in homeostasis -infection, inflammation, tissue injury, neoplasm, or immune disturbance. The activation of the acute phase response, signaled by interleukin-6, produces proteins (fibrinogen, C-reactive protein (CRP), serum amyloid A) that lead to inflammatory reactions. The tissues themselves contain elevated levels of acute phase proteins and cytokines resulting in a localized inflammatory effect. Localized inflammatory responses in the intimal layer of the arterial wall have been shown to be responsible for many of the aspects of intimal thickening and plaque disruption, leading to acute cardiovascular events. The predictive value of plasma C-reactive protein as a risk factor for cardiovascular events has led some researchers to support the use of CRP as a main cardiovascular risk assessment tool, along with total cholesterol:HDL ratios and homocysteine levels. The ability of HMG-CoA reductase inhibitors to lower C-reactive protein levels has recently brought into question the mechanisms of action of the statin drugs. Because these medications lower incidences of acute cardiovascular events as well as decreasing morbidity and mortality well before the effects of lowered LDL cholesterol can be expected to occur, questions have been asked about whether they may work independently of LDL-lowering mechanisms. Red yeast rice contains a naturally-occurring statin (lovastatin) as well as other cholesterol-lowering compounds, some with antioxidant effects. Alpha-tocopherol also significantly lowers CRP levels in diabetics and nondiabetics, and minimizes other aspects of the acute phase response and inflammatory damage involved in atherosclerosis. This may account for alpha-tocopherol's positive effect on cardiovascular morbidity and mortality. Finally, polyphenolic compounds present in virgin olive oil also have anti-inflammatory and antioxidative effects in cardiovascular disease. The phenolic compounds in virgin olive oil may explain some of the protective effects found in epidemiological studies.
 ...
PMID:Cardiovascular disease: C-reactive protein and the inflammatory disease paradigm: HMG-CoA reductase inhibitors, alpha-tocopherol, red yeast rice, and olive oil polyphenols. A review of the literature. 1141 71

Mortality is markedly elevated in patients with end-stage renal disease. The leading cause of death is cardiovascular disease. Lipoprotein levels are only slightly elevated in dialysis patients, and cardiovascular risk is inversely correlated with serum cholesterol, suggesting that a process other than hyperlipidemia plays a role in the incidence of cardiovascular disease. Hypoalbuminemia, ascribed to malnutrition, has been one of the most powerful risk factors that predict all-cause and cardiovascular mortality in dialysis patients. The presence of inflammation, as evidenced by increased levels of specific cytokines (interleukin-6 and tumor necrosis factor alpha) or acute-phase proteins (C-reactive protein and serum amyloid A), however, has been found to be associated with vascular disease in the general population as well as in dialysis patients. The process of inflammation, also called the acute-phase response, additionally causes loss of muscle mass and changes in plasma composition-decreases in serum albumin, prealbumin, and transferrin levels, also associated with malnutrition. Inflammation alters lipoprotein structure and function as well as endothelial structure and function to favor atherogenesis and increases the concentration of atherogenic proteins in serum, such as fibrinogen and lipoprotein (a). Inflammation in dialysis patients is episodic. The causes are likely to be multifactorial and include vascular access infection, less-than-sterile dialysate, dialysate back leak, and nonbiocompatible membranes in addition to clinically apparent infection. In addition, proinflammatory compounds, such as advanced glycation end products, accumulate in renal failure, and defense mechanisms against oxidative injury are reduced, contributing to inflammation and to its effect on the vascular endothelium.
 ...
PMID:The microinflammatory state in uremia: causes and potential consequences. 1142 86

Although fibrinogen genes are expressed constitutively in hepatocytes, their transcription can be greatly increased during inflammatory stress. Extensive studies have focused on the cytokine mediated transcriptional regulation of fibrinogen genes. It is clear that interleukin-6 (IL-6) and its family of cytokines are the major inducers of fibrinogen gene expression. Functional analyses of all three fibrinogen promoters for human and rat all demonstrate that the conserved CTGGGAA motifs within the proximal promoter of each fibrinogen gene are the IL-6 responsive elements. Exploration of the rat gamma fibrinogen gene demonstrated that the IL-6 activated transcription factor, STAT3, binds to the CTGGGAA motif and is required for the IL-6 mediated upregulation of this gene. IL-6 mediated fibrinogen production can be significantly elevated by glucocorticoid treatment. The synergistic effect of glucocorticoids and IL-6 relies on the functional interaction between STAT3 and glucocorticoid receptor. In addition to the upregulation signals for fibrinogen gene expression during inflammatory stress, other signaling also downregulates the expression of fibrinogen genes. For example, the proinflammatory cytokine IL-1 beta exerts inhibitory function on IL-6 mediated fibrinogen gene expression. Given the fact that elevated levels of fibrinogen in blood correlate with increased risk for cardiovascular disease, there is strong motivation to explore the molecular mechanisms that control fibrinogen expression, especially those signals that may downmodulate expression and thus provide novel approaches to controlling fibrinogen levels.
 ...
PMID:Transcriptional control mechanism of fibrinogen gene expression. 1146 May 5

This study set out to clarify whether the inhibition of sterol or nonsterol derivatives arising from mevalonate biotransformation plays a major role in the in vivo anti-inflammatory action of statins. Hepatic synthesis of all these derivatives was inhibited in mice by administered statins, whereas squalestatin inhibited only sterol derivatives. Using a short-term treatment schedule, we found that statins reduced the hepatic activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase without affecting blood cholesterol. This treatment inhibited lipopolysaccharide- and carrageenan-induced pouch leukocyte recruitment and the exudate production of interleukin-6, monocyte chemotactic protein-1, and RANTES. Coadministration of mevalonate reversed the effect of statin on leukocyte recruitment. The inhibition of sterol synthesis by squalestatin did not have any anti-inflammatory effect, indicating that the biosynthesis of nonsterol compounds arising from mevalonate is crucial for the in vivo regulation of cytokine and chemokine production by statins. Their inhibition by statins may account for the reported anti-inflammatory effects of these drugs and may provide a biochemical basis for the recently reported effects of statins in the prevention of cardiovascular disease and mortality.
 ...
PMID:In vivo anti-inflammatory effect of statins is mediated by nonsterol mevalonate products. 1149 48

Sidestream cigarette smoke (SSCS) makes up about 85% of significantly toxic environmental tobacco smoke (ETS). Reactive oxygen species (ROS) in SSCS play an important role in the pathogenesis of a wide range of diseases. Interleukin-6 is a pro-inflammatory cytokine and is closely linked with pathology in cardiovascular disease and conditions that have an inflammatory base. Exposure to SSCS through a burning cigarette for 30 min/day, 5 days a week, for 4 months increased interleukin-6 production in spleen and lipid peroxide level in mouse liver. Our findings suggest that ROS induced by SSCS will promote hepatic lipid peroxidation and may also contribute to an increase in interleukin-6 cytokine production. Multiple antioxidants given as a dietary supplement significantly normalized interleukin-6 cytokine production and prevented hepatic lipid peroxidation. We conclude that the SSCS in moderate intake levels increased oxidation and promoted inflammatory cytokine interleukin-6 production, whereas antioxidants prevented these changes.
 ...
PMID:Antioxidant supplementation prevents oxidation and inflammatory responses induced by sidestream cigarette smoke in old mice. 1167 65

As renal function declines, the prevalence of both malnutrition and cardiovascular disease increase. Both malnutrition and vascular disease correlate with the levels of markers of inflammation both in patients treated with dialysis and in those not yet on dialysis. While it is possible that the markers of inflammation (increased levels of C-reactive protein (CRP) or interleukin-6 (IL-6)) are a result of inflammation arising from the atherosclerotic process, changes in endothelial cell gene expression, in plasma protein composition and in lipoprotein structure that arise from inflammation are likely to be atherogenic. The causes of inflammation are likely to be multifactorial. CRP levels are associated with cardiovascular risk in the general population and decrease following treatment with HMG-CoA reductase inhibitors. It is speculated that use of these agents or directly suppressing inflammation may have use in treating the inflammatory-malnutrition syndrome in dialysis patients.
 ...
PMID:Role of inflammation and its treatment in ESRD patients. 1180 62

Dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) are weak androgens produced primarily by the adrenal gland. Although their plasma concentrations by far exceed those of any other adrenal product, their physiological roles have not yet been determined. In plasma, where the major portion of these hormones is present in the sulfate form, it is possible that DHEAS serves as a reservoir for DHEA. Since various tissues have been shown to contain steroid sulfatases. The peak plasma levels of DHEA and DHEAS occur at approximately age 25 years, decrease progressively thereafter, and diminish by 95 per cent around the age of 85 years. The decline of DHEAS concentrations with aging has led to the suggestion that DHEAS could play a role in itself and be implicated in longevity. Moreover, the epidemiological evidence has shown that adult men with high plasma DHEAS levels are less likely to die of cardiovascular disease. DHEA has also been shown to increase the body's ability to transform food into energy and burn off excess fat. Another recent finding involves the anti-inflammatory properties of DHEA. It has been known that DHEA can lower the levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha). It should be pointed out that chronic inflammation is known to play a critical role in the development of the killer diseases of aging: heart disease, Alzheimer's disease and certain types of cancer. In conclusion, DHEA or DHEAS administration combined with conventional treatment may be implicated in particular conditions to improve the quality of life.
 ...
PMID:DHEA(S): the fountain of youth. 1185 89

Atherosclerotic plaques were likened histologically to healing inflammatory lesions by Russell Ross, who proposed a "response to injury" hypothesis for their formation. More recently, intraplaque inflammation has been postulated to play a role in thinning of the fibrous cap, plaque rupture, and superadded thrombosis. Potential causes for vascular injury include mechanical stress, smoke exposure, hypercholesterolemia, hyperhomocysteinemia, and chronic infection (direct, or indirect). Blood levels of inflammatory markers (e.g., C-reactive protein [CRP]; serum amyloid A [SAA]; fibrinogen; plasma viscosity; erythrocyte sedimentation rate [ESR]; leukocyte count, low serum albumin) have been associated with vascular risk factors and with prevalent and incident atherothrombotic cardiovascular disease (CVD) (coronary heart disease, [CHD]; stroke; and peripheral arterial disease). More recently, cytokines (e.g., interleukin-6 [IL-6]) and soluble adhesion molecules (e.g., intercellular adhesion molecule-1, vascular cell adhesion molecule-1) have been associated with both risk factors and disease; and offer potential therapeutic targets for nonspecific "anti-inflammatory" treatment of arterial disease. Infections associated with arterial disease include specific infections (Chlamydia pneumoniae, Helicobacter pylori) and nonspecific infections (periodontal infections, respiratory tract infections). Recent meta-analyses have shown that associations of serum markers of C. pneumoniae and H. pylori with arterial disease, risk factors, or potential intermediary mechanisms for disease are weaker than was first suggested by early reports. Likewise, further studies and meta-analyses are required to evaluate the epidemiologic relationships of CVD to periodontal infection and disease and to chronic pulmonary infections and disease. The weaker the associations between chronic infections and CVD, the larger is the size of randomized controlled trials required to establish (or exclude) a preventive effect of infection treatment. While control of chronic infection in the mouth, stomach or lungs is appropriate for its local effects, proving its efficacy in prevention of CVD presents a continuing challenge to medical science.
 ...
PMID:The relationship between infection, inflammation, and cardiovascular disease: an overview. 1188 52

Leptin is synthesized in adipocytes and acts primarily through central pathways suppressing appetite and increasing the metabolic rate in rodents as well as in humans. Recently leptin has also been suggested to have peripheral effects and be involved in insulin action. Since cytokines and chemokines may have effects on appetite regulation as well as on some of the obesity-related complications e.g. insulin resistance and cardiovascular disease, we investigated the effects of various cytokines and chemokines on leptin production in human adipose tissue fragments in vitro. Abdominal subcutaneous adipose tissue from healthy normal to overweight females was incubated for up to 48 h with the cytokines: tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) and the chemokine: interleukin-8 (IL-8). IL-1beta (50 ng/ml) and TNF-alpha (10 ng/ml) decreased leptin production by 30-50% (P<0.05) and gene expression by 80-90% (P<0.05). In contrast, IL-6 and IL-8 had no effect on either leptin production or leptin gene expression. Interestingly, IL-1beta elicited a biphasic effect on leptin release with an incremental phase observed within 4 h with no concomitant change in leptin gene expression, followed by a long-lasting inhibition of leptin release and leptin gene expression. This could suggest that IL-1beta through a post-translational pathway induced an acute increase in leptin-secretion, perhaps through the release of leptin from a pre-formed pool within the adipose tissue. The long-term decrease in both leptin secretion and transcription could indicate that pro-inflammatory cytokines such as IL-1beta and TNF-alpha might influence the circulating leptin levels and thereby influence the adipose tissue to brain signalling, which could be of importance in relation to the obesity-associated diseases such as insulin resistance and cardiovascular disease.
 ...
PMID:Effects of pro-inflammatory cytokines and chemokines on leptin production in human adipose tissue in vitro. 1199 82


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>