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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ciliary neurotrophic factor (CNTF), a member of the interleukin-6 (IL-6) superfamily, has recently been shown to induce several inflammatory responses when administered to healthy animals, including induction of fever and a hepatic acute phase protein response. In the present report, 250 micrograms.kg body wt-1.day-1 of recombinant rat CNTF or murine IL-6 were repeatedly administered to healthy mice over a 7-day period in an effort to compare biological responses. In addition to its in vivo capacity to elicit a hepatic acute phase response, administration of CNTF, but not IL-6, produced profound anorexia and lean tissue wasting in mice. In C57B1/6 mice, 7 days of CNTF administration led to a 21% loss in carcass protein content, resulting from carcass protein breakdown rates being increased 218% over freely fed controls (both P < 0.01). Protein synthesis rates in carcass protein were also increased in CNTF-treated mice compared with both freely fed animals and mice pair-fed equivalent quantities of food. In contrast, administration of equivalent quantities of murine IL-6 had no effect on food intake or body weight in mice, although IL-6 produced a similar hepatic acute phase response, as determined by increases in serum amyloid P and seromucoid fraction and increases in total hepatic protein synthesis. However, when CNTF was coincubated with extensor digitorum longus muscles from juvenile rats in vitro, rates of total muscle and myofibrillar protein degradation and muscle protein synthesis were unchanged. We conclude that CNTF can regulate in vivo both skeletal muscle remodeling as well as the distant anorexia and hepatic acute phase protein responses. In the case of skeletal muscle, these actions are both indirect and independent of the associated anorexia. These properties of CNTF are distinct from IL-6, which when administered to the mouse at these doses is neither anorexigenic nor cachexia producing.
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PMID:Ciliary neurotrophic factor is catabolic and shares with IL-6 the capacity to induce an acute phase response. 876 Feb 19

We report a patient with metastatic adenocarcinoma of the lung who had a detectable serum interleukin-6 (IL-6) level. Despite systemic chemotherapy, the tumor progressed, with elevation of serum IL-6 level. Palliative steroid therapy with 20 mg/day of prednisolone resulted in the decline of serum IL-6 level and, simultaneously, improved anorexia and oral intake. Although there was no weight gain or improvement in hypoalbuminemia, these results suggest that steroids may suppress the abnormal production of IL-6 in cancer patients and that this action affects symptoms. Further study is warranted to clarify the role of IL-6 in tumor-related symptoms and the effect of steroid therapy in relation to IL-6 production in cancer patients.
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PMID:Palliative steroid therapy and serum interleukin-6 levels in a patient with lung cancer. 880 83

Interleukin-1 (IL-1) and interleukin-6 (IL-6) are thought to play a role in mediating weight loss, net protein catabolism, anorexia, and fever after infection or injury. Because IL-1 and IL-6 can be synthesized in the brain and have been shown to be increased in central nervous system (CNS) infections, we investigated the metabolic consequences of prolonged CNS exposure to these cytokines. At equivalent doses, intracerebroventricular infusion of IL-1, but not IL-6, caused negative nitrogen balance, weight loss, and anorexia. Intracerebroventricular infusion of IL-1 also caused adrenocortical activation, as indicated by increased adrenal weight and plasma corticosterone, and decreased thymus weight. However, clamping plasma glucocorticoids at low levels by adrenalectomy and corticosterone pellet replacement did not attenuate IL-1-induced losses of body weight and nitrogen. We conclude that centrally produced IL-1 could play an important role in the metabolic alterations associated with CNS injury or infection and that these effects may not be solely attributable to increased secretion of glucocorticoids.
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PMID:Chronic central nervous system exposure to interleukin-1 beta causes catabolism in the rat. 894 46

Interleukin-6 (IL-6), among other cytokines, is thought to be involved in the regulation of sickness behavior (e.g., anorexia, cachexia, fever, and lethargy) induced by infections bacterial and viral origin) and sterile tissue necrosis (burns and surgical traumas). Mice deficient in IL-6 (IL-6 KO) were generated by gene targeting. Homozygous IL-6 KO male and female mice and their appropriate controls were implanted with biotelemeters to monitor body temperature (Tb) and motor activity (Act). Normal circadian rhythms in Tb and Act as well as rates of food intake and weight gain did not differ significantly between sex-matched IL-6 KO and control groups at 30 degrees C in a 12:12-h light-dark cycle. Sterile tissue damage was induced in mice by subcutaneous injection of turpentine (0.1 ml, left hindlimb). Influenza pneumonitis was induced by intranasal inoculation of mouse-adapted influenza A virus (17.5 plaque-forming units). Lack of IL-6 completely prevented fever, anorexia, and cachexia because of turpentine abscess in both sexes. It did not prevent lethargy, although IL-6 KO mice recovered to normal Act significantly sooner than wild-type mice. Symptoms of sickness were only slightly modified during influenza virus infection in IL-6 KO mice. Attenuation of sickness behavior was more pronounced in IL-6 KO female than in male mice. We conclude that, although IL-6 is induced during both turpentine abscess and influenza infection, this cytokine appears to be more critical in induction of the symptoms of sickness behavior during sterile tissue abscess than during influenza infection.
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PMID:Sickness behavior in mice deficient in interleukin-6 during turpentine abscess and influenza pneumonitis. 912 87

Prolonged production of cytokines associated with cancer and chronic infections, and other long-term immune reactions is increasingly recognized as a main causal factor of the often severe signs and symptoms that accompany these diseases: weight loss, anorexia, and metabolic breakdown termed cachexia. The cytokine that initially was held responsible for causing these changes was tumor necrosis factor (TNF). However, from various studies it has become clear that the action of TNF can only be understood in the context of simultaneous presence of other cytokines, some of which have activities that are at the least equally important as TNF in bringing about cachexia. This review summarizes the experimental evidence for the involvement of cytokines in the pathogenesis of cachexia. Indirect evidence comes from the observation that cachexia can be induced in animals by repeated injections of cytokines or by inoculation of cytokine-producing cells. Thus, cachexia has been described in mice inoculated with tumor cells carrying and expressing genes for either TNF, interleukin-6 (IL-6), leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF) and interferon-gamma (IFN-gamma). More direct evidence is provided by the observations that cachexia in experimental animal models can be mitigated by administration of specific antagonists of cytokines. These latter type of studies revealed that cachexia can rarely, if ever, be attributed to one single cytokine but rather to a set of cytokines that work in concert in cachexia. A pool of anticytokine antibodies or other cytokine inhibitors might, therefore, be considered as a potential intervention for the treatment of cachectic patients, but this approach may induce immunosuppression, and, therefore, danger exists that such treatment may benefit the infectious agent or tumor.
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PMID:Cytokines and cachexia. 929 87

The child with a malignancy frequently will have associated cachexia with significant weight loss and malnutrition. The reasons for this are multifactorial and may be related directly to the tumor, such as increased metabolic rate, circulating peptides leading to anorexia, and decreased intake due to poor appetite or gut involvement. There appears to be other reasons involved, including increased whole body protein breakdown, increased lipolysis, and increased gluconeogenesis. Release of certain cytokines, such as tumor necrosis factor, interleukin-1, interleukin-6, and others may increase the cancer cachexia. Malnutrition in these children leads to intolerance of chemotherapy and radiotherapy as well as increased local and systemic infections. For many years, oncologists were hesitant to provide nutrition support to cancer patients for fear that tumor growth would be enhanced. Pediatric oncologists learned early that starvation plays no positive role in cancer therapy. Adjunctive nutritional support, either enterally or parenterally, supports the patient during therapy with surgery, chemotherapy, or radiation. Many studies have now shown that the nutritionally replete patient tolerates therapy better and in some pediatric malignancies may enhance survival.
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PMID:Nutritional support of the pediatric oncology patient. 943 98

Interleukin-6, an inflammatory cytokine, is characterized by pleiotropy and redundancy of action. Apart from its hematologic, immune, and hepatic effects, it has many endocrine and metabolic actions. Specifically, it is a potent stimulator of the hypothalamic-pituitary-adrenal axis and is under the tonic negative control of glucocorticoids. It acutely stimulates the secretion of growth hormone, inhibits thyroid-stimulating hormone secretion, and decreases serum lipid concentrations. Furthermore, it is secreted during stress and is positively controlled by catecholamines. Administration of interleukin-6 results in fever, anorexia, and fatigue. Elevated levels of circulating interleukin-6 have been seen in the steroid withdrawal syndrome and in the severe inflammatory, infectious, and traumatic states potentially associated with the inappropriate secretion of vasopressin. Levels of circulating interleukin-6 are also elevated in several inflammatory diseases, such as rheumatoid arthritis. Interleukin-6 is negatively controlled by estrogens and androgens, and it plays a central role in the pathogenesis of the osteoporosis seen in conditions characterized by increased bone resorption, such as sex-steroid deficiency and hyperparathyroidism. Overproduction of interleukin-6 may contribute to illness during aging and chronic stress. Finally, administration of recombinant human interleukin-6 may serve as a stimulation test for the integrity of the hypothalamic-pituitary-adrenal axis.
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PMID:The pathophysiologic roles of interleukin-6 in human disease. 944 73

During infection and injury a series of metabolic events are activated that leads to a state of negative nitrogen balance and significant loss of lean body mass. This process is characterized by marked anorexia, net whole body protein breakdown, and liver anabolism. This host response initially is beneficial to the body because it helps it to fight disease and enhance healing. However, if such imbalance is maintained for long periods, it will invariably produce significant loss of lean body mass that may lead to a series of untoward clinical events. The role of the proximate cytokines, tumor necrosis factor (TNF), interleukin-1 (IL-1), and interleukin-6 (IL-6) as well as glucocorticoids as important mediators of many pathophysiological manifestations of infection and injury has been studied extensively. However, the involvement of other mediators, at least in skeletal muscle proteolysis during sepsis has been hypothesized, because blockade of glucocorticoids, TNF, IL-1, and IL-6 reduces but does not normalize protein breakdown rates nor does the direct application of these mediators to skeletal muscle in vitro enhance proteolysis. Furthermore other studies have suggested that the lymphokine, interferon-gamma (IFN-gamma, type II interferon or immune interferon), produces fever and enhances thermogenesis, body weight loss, and skeletal muscle depletion in rodents in a manner similar to that seen with TNF and IL-1. Cytokines appear to be major components of the host metabolic response during infection and injury. However, neither all the cytokines involved nor the exact mechanisms underlying their metabolic effects are completely understood. The regulation of muscle protein synthesis and breakdown, which largely determines the development of cachexia, appears to depend on the delicate balance between a number of regulatory substances including cytokines, glucocorticoids, catecholamines, insulin, and insulin-like growth factors.
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PMID:The role of cytokines in the catabolic consequences of infection and injury. 1008 3

Cytokines, such as tumor necrosis factor (TNF) and interleukin-6, may contribute to the anorexia and cachexia of infection, cancer, and AIDS. The present study tests the hypothesis that endotoxin alters the expression of two key fat cell proteins, leptin and beta3-adrenergic receptor (beta3-AR), through a mechanism involving TNF-alpha. Increasing doses of Escherichia coli endotoxin (lipopolysaccharide, LPS) resulted in dose-dependent elevations of plasma leptin (maximal response approximately 7-fold, half-maximal effective dose of approximately 16 microg/100 g body wt) and white fat leptin mRNA in C3/HeOUJ mice. LPS also produced a large decrease in adipose tissue beta3-AR mRNA and a parallel reduction in beta-agonist-induced activation of adenylyl cyclase. Changes in plasma leptin and beta3-AR mRNA were preceded by an approximately threefold increase in white fat TNF mRNA. TNF administration resulted in changes similar to those seen with LPS. We conclude that endotoxemia results in an induction of leptin mRNA and a decrease in beta3-AR mRNA in adipose tissue, an effect that may be mediated by alterations in TNF-alpha.
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PMID:Endotoxin-induced alteration in the expression of leptin and beta3-adrenergic receptor in adipose tissue. 961 Nov 47

Leptin, a 16-kDa protein secreted from white adipocytes, has been implicated in the regulation of food intake, energy expenditure, and whole-body energy balance in rodents and humans. The gene encoding leptin was identified by positional cloning and is the mutation leading to the profound obese phenotype of the ob/ob mouse. Exogenous administration of leptin to ob/ob mice leads to a significant improvement in reproductive and endocrine status as well as reduced food intake and weight loss. The expression and secretion of leptin is highly correlated with body fat mass and adipocyte size. Cortisol and insulin are potent stimulators of leptin expression, and expression is attenuated by beta-adrenergic agonists, cAMP, and thiazolidinediones. The role of other hormones and growth factors in the regulation of leptin expression and secretion is emerging. Leptin circulates specifically bound to proteins in serum, which may regulate its half-life and biological activity. Isoforms of the leptin receptor, members of the interleukin-6 cytokine family of receptors, are found in multiple tissues, including the brain. Many of leptin's effects on food intake and energy expenditure are thought to be mediated centrally via neurotransmitters such as neuropeptide Y. Multiple peripheral effects of leptin have also been recently described, including the regulation of insulin secretion by pancreatic beta cells and regulation of insulin action and energy metabolism in adipocytes and skeletal muscle. Leptin is thought to be a metabolic signal that regulates nutritional status effects on reproductive function. Leptin also plays a major role in hematopoeisis and in the anorexia accompanying an acute cytokine challenge. The profound effects of leptin on regulating body energy balance make it a prime candidate for drug therapies for humans and animals.
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PMID:The biology of leptin: a review. 962 47


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