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)

Sarcopenia is a term utilized to define the loss of muscle mass and strength that occurs with aging. Sarcopenia is believed to play a major role in the pathogenesis of frailty and functional impairment that occurs with old age. Progressive muscle wasting occurs with aging. The prevalence of clinically significant sarcopenia is estimated to range from 8.8% in young old women to 17.5% in old old men. Persons who are obese and sarcopenic (the "fat frail") have worse outcomes than those who are sarcopenic and non-obese. There is a disproportionate atrophy of type IIa muscle fibers with aging. There is also evidence of an age-related decrease in the synthesis rate of myosin heavy chain proteins, the major anabolic protein. Motor units innervating muscle decline with aging, and there is increased irregularity of muscle unit firing. There are indications that cytokines-especially interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6-play a role in the pathogenesis of sarcopenia. Similarly, the decline in anabolic hormones-namely, testosterone, dehydroepiandrosterone growth hormone, and insulin-like growth factor-I-is also implicated in the sarcopenic process. The role of the physiologic anorexia of aging remains to be determined. Decreased physical activity with aging appears to be the key factor involved in producing sarcopenia. An increased research emphasis on the factors involved in the pathogenesis of sarcopenia is needed.
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PMID:Sarcopenia. 1128 18

Previous research has shown that reductions in body weight prior to induction of acute inflammation can attenuate inflammation-induced anorexia in male rats. In the current study, potential mechanisms responsible for this observation were examined. Specifically, the effect of a 12% prior reduction in body weight on serum leptin, insulin, and corticosterone; levels of interleukin-1 (IL-1), interleukin-6 (IL-6) in the serum, liver, and spleen; neuropeptide Y (NPY) and POMC mRNA levels in the arcuate nucleus (ARC) of the hypothalamus were examined 8 h after induction of acute inflammation. Rats with prior weight reduction had significantly lower serum leptin levels and gene expression of POMC in the ARC than normal-weight rats. In contrast, prior weight reduction altered neither NPY mRNA in the ARC, nor IL-1alpha, IL-1beta, and IL-6 levels in the serum, liver, and spleen. These results suggest that the attenuation of inflammation-induced anorexia by prior weight reduction is not due to altered cytokine activity, but rather to changes in energy regulatory systems that moderate the anorexic actions of IL-1beta and IL-6. One potential change may be reduced activity of the CNS melanocortin system induced by decreased circulating leptin.
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PMID:Activity of body energy regulatory pathways in inflammation-induced anorexia. 1149 55

Interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) induce anorexia, and multiple behavioral and biochemical alterations that mimic those of anorexia nervosa. Reports in the literature, however, contain contrasting data on the pattern of secretion of the three cytokines and on the downstream activities of their receptors and receptor antagonists in anorexia nervosa. We measured plasma concentrations of IL-1beta, IL-6, TNF-alpha, soluble IL-6 receptor (sIL-6-R), soluble TNF-alpha receptors I and II (s-TNF-alpha-R-I and II), and soluble IL-1beta receptor antagonist (s-IL-1beta-R-A) in 14 female patients with anorexia nervosa (nine restricters, five binge/purgers) and in 13 age- and sex-matched healthy control subjects to see whether the circulating cytokine concentrations and the downstream steps of cytokine activity were impaired, and if these alterations were correlated with some aspects of the disease. Concentrations of IL-1beta, IL-6, TNF-alpha, s-TNF-alpha-R-I and -II and sIL-1beta-RA in plasma did not differ significantly in patients with anorexia nervosa compared with control subjects. Concentrations of sIL-6-R were significantly lower in the patients than in the control subjects, but there were no differences between the two sub-types of anorexia nervosa. The etiopathogenetic significance of the sIL-6-R alteration is not clear, but together with recent data in the literature on cytokine function, the finding suggests that an impairment of the pro-inflammatory cytokine pathway might be involved in the development of anorexia nervosa.
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PMID:Plasma concentrations of interleukin-1-beta, interleukin-6 and tumor necrosis factor-alpha, and of their soluble receptors and receptor antagonist in anorexia nervosa. 1154 99

Megestrol acetate improves appetite and abrogates weight loss in some patients with advanced cancer. Moreover, preliminary studies suggest that progestational agents down-regulate interleukin-6 (IL-6), an inflammatory cytokine widely implicated in cancer-associated anorexia and weight loss. The present investigation examined the effects of megestrol acetate on IL-6 in an attempt to confirm these earlier, preliminary studies. The translational component of a large multi-institutional trial, this investigation examined 85 patients with advanced cancer and weight loss. Patients had been randomly assigned to receive megestrol acetate liquid suspension 800 mg/day + placebo tablets, or oral dronabinol tablets 2.5 mg b.i.d. + liquid placebo, or both agents. Other testing included serial physician-reported weight and patient-reported appetite and global quality of life. We found no significant differences in 1-month changes in serum IL-6 according to whether patients had been treated with megestrol acetate, dronabinol, or the combination: the mean differences +/- standard deviation were -1.52+/-4.7 pg/ml, -0.62+/-3.5 pg/ml, and -0.2+/-3.1 pg/ml, respectively (P=0.40, by one-way ANOVA). Among the patients who noted alterations in their appetite over 1 month, we observed no significant changes in IL-6. Finally, changes in serum IL-6 were not associated with shifts in weight or global quality of life. Our investigation provides no evidence that megestrol acetate down-regulates IL-6 in patients with cancer-associated anorexia and weight loss.
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PMID:Does megestrol acetate down-regulate interleukin-6 in patients with cancer-associated anorexia and weight loss? A North Central Cancer Treatment Group investigation. 1232 13

Under normal conditions, the homeostasis of energy intake is maintained in the hypothalamus by 1) transducing metabolic and sensorial inputs arising from the periphery into neuronal response, 2) integrating the information originating from different tissues, and 3) triggering the appropriate feeding responses. If cancer anorexia is considered a disruption of the physiologic mechanisms controlling energy intake, it is conceivable that its pathogenesis may lie in an abnormal input of information to the hypothalamus, its defective transduction and integration, or the induction of exaggerated and inappropriate feeding responses. Currently available data suggest that the pathogenesis of cancer anorexia is multifactorial and involves most of the neuronal signaling pathways modulating energy intake. Thus, a number of factors has been proposed as putative mediators of cancer anorexia, including hormones (e.g., leptin), neuropeptides (e.g., neuropeptide Y), cytokines (e.g., interleukin-1, interleukin-6, tumor necrosis factor), and neurotransmitters (e.g., serotonin and dopamine). However, it is unlikely that they represent separate and distinct pathogenic mechanisms; rather, it appears that close interrelationships may exist among them. In line with this reasoning, consistent experimental and human data suggest that hypothalamic monoaminergic neurotransmission and serotonergic activity in particular may represent a major target on which different anorexia-related factors converge. Thus, interfering pharmacologically with hypothalamic serotonin synthesis and activity has been tested as a therapeutic strategy in anorectic cancer patients with encouraging results. However, more clinical options will be available by revealing the complex interactions between the many factors participating in controlling energy intake under normal and pathologic conditions. Further, modulation of hypothalamic activity also might result in reduced catabolic signals to skeletal muscles, thus improving the cachexia associated with cancer.
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PMID:Neurochemical mechanisms for cancer anorexia. 1182 80

Anorexia and weight loss are frequent complications of acute and chronic infections and result from induction of cytokines, prostaglandins, and other inflammatory mediators that are critical for pathogen elimination. Selective attenuation of the hypophagic response to infection and maintenance of the production of factors essential for infection control would be a useful addition to antimicrobial therapy in the treatment of human disease. Here, we evaluate the relative contribution of cyclooxygenase (COX)-1- and COX-2-derived prostaglandins to anorexia and weight loss precipitated by systemic immune activation by lipopolysaccharide (LPS). Using COX isoform-selective pharmacological inhibitors and gene knockout mice, we found that COX-2 inhibition during LPS-induced inflammation results in preserved food intake and maintenance of body weight, whereas COX-1 inhibition results in augmented and prolonged weight loss. Regulation of neuropeptide Y, corticotropin-releasing hormone, leptin, and interleukin-6 does not change as a function of COX-2 inhibition after LPS administration. Our data implicate COX-2 inhibition as a therapeutic target to maintain nutritional status while still allowing a normal cytokine response during infection.
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PMID:COX-2 inhibition attenuates anorexia during systemic inflammation without impairing cytokine production. 1183 69

C-reactive protein (CRP) is a nonspecific but sensitive marker of inflammation. Interleukin-6 (IL-6), IL-1, and tumor necrosis factor alpha induce the synthesis of CRP in hepatocytes. Increased CRP level is considered to be an important risk factor for atherosclerosis, myocardial infarction, peripheral vascular disease, and ischemic stroke. It is positively correlated with weight loss, anorexia-cachexia syndrome, extent of disease, and recurrence in advanced cancer. Its role as a predictor of survival has been shown in multiple myeloma, melanoma, lymphoma, ovarian, renal, pancreatic, and gastrointestinal tumors. Measurement of CRP is simple, cheap, and routine and provides valuable information in palliative care.
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PMID:The role of C-reactive protein as a prognostic indicator in advanced cancer. 1193 16

The Prognostic Inflammatory Nutritional Index (PINI) is a simple scoring system that has been used to evaluate nutritional status and prognosis in critically ill patients. The PINI has never been evaluated in advanced cancer. Fifty consecutive patients with advanced cancer, weight loss, and anorexia were studied. C-reactive protein (CRP), albumin, pre-albumin, interleukin-6 (IL-6), and alpha 1-acid glycoprotein (AAG) were evaluated. The individual values for AAG, CRP, and IL-6 were markedly elevated. In contrast to albumin and prealbumin, CRP levels were very high. The PINI was significantly elevated, and higher than reported in critically ill intensive care patients. Elevated IL-6 levels correlated with high PINI and CRP values. CRP, IL-6, and PINI should be considered in future research on nutritional status and prediction of prognosis in advanced cancer.
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PMID:Assessment of nutritional status and prognosis in advanced cancer: interleukin-6, C-reactive protein, and the prognostic and inflammatory nutritional index. 1274 90

Data from both rodent models and humans suggest that intact neuronal melanocortin signaling is essential to prevent obesity, as mutations that decrease the melanocortin signal within the brain induce hyperphagia and excess body fat accumulation. Melanocortins are also involved in the pathogenesis of disorders at the opposite end of the spectrum of energy homeostasis, the anorexia and weight loss associated with inflammatory and neoplastic disease processes. Studies using melanocortin antagonists (SHU9119 or agouti-related peptide) or genetic approaches (melanocortin-4 receptor null mice) suggest that intact melanocortin tone is required for anorexia and weight loss induced by injected lipopolysaccharide (an inflammatory gram-negative bacterial cell wall product) or by implantation of prostate or lung cancer cells. Although the precise mechanism whereby peripheral inflammatory/neoplastic factors activate the melanocortin system remains unknown, the proinflammatory cytokines (interleukin-1, interleukin-6, and tumor necrosis factor-alpha) that are produced in the hypothalamus of rodents during both inflammatory and neoplastic disease processes likely play a role. The data presented in this paper summarize findings that implicate neuronal melanocortin signaling in inflammatory anorexia.
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PMID:Melanocortin signaling and anorexia in chronic disease states. 1285 26

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


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