Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:021712 (IL-6)
 58,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this report we describe an experimental model of cachexia that fulfills the criteria of an early effect with a small tumor mass not related to the growth rate of the tumor, and progressive wasting of muscle and fat without a detectable loss of appetite. C-26.IVX is a cell line derived from murine colon-26 adenocarcinoma which retains the transplantability of the original tumor and induces true cachexia in syngeneic hosts. Evidence is presented to support a role for interleukin (IL-6) as a cachectic factor in the development of cancer cachexia in this model system. Thus, increasing levels of IL-6 in C-26.IVX-bearing mice correlate with the development of cachexia. If the primary tumors were resected, mice gained weight and the levels of IL-6 in the serum were reduced significantly. Moreover, monoclonal antibody to murine IL-6 (but not anti-tumor necrosis factor antibody) was able to significantly suppress the development of key parameters of cachexia in tumor bearing mice.
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PMID:Evidence for the involvement of interleukin 6 in experimental cancer cachexia. 156 7

Human recombinant IL-1 beta was able to kill C3H/HeJ mice only when inoculated intravenously at very high doses. IL-1 beta, inoculated at 100 mg/kg i.v. as a bolus, induced a shock-like state characterized by anorexia, severe hypothermia and hypoglycemia and persistent neutrophilia, leading to death in 55% of animals generally between 24 and 48 h. In contrast, the noninflammatory adjuvant IL-1 beta peptide VQGEESNDK (position 163-171) did not induce any toxic effect in vivo, when administered following the same schedule. At variance with what was previously observed in endotoxin induced shock, IL-1 beta induced death was not preceded by appearance of circulating TNF. On the other hand, very high and persistent levels of circulating IL-6 could be detected after lethal IL-1 beta administration. Treatment of mice with ibuprofen or with chlorpromazine, both known to counteract some of the toxic effects of IL-1 in vivo, could protect from IL-1 beta induced mortality. Both drugs, at doses protecting from IL-1 beta induced death, were able to abolish IL-1 beta-induced rise of circulating phospholipase A2 (PLA2) activity, and the subsequent generation of toxic PLA2-derived metabolites.
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PMID:Mechanism of acute toxicity of IL-1 beta in mice. 187 93

A traditional view has been that bacterial products, such as endotoxins from gram negative bacteria, have a direct deleterious effect on the host, resulting in fever, hypermetabolism, anorexia, and tissue damage. In recent years, however, it has been shown that endogenous products of the host, secreted by macrophages and other cellular elements of the immune system, act as mediators in activating the metabolic and other physiological changes characteristic of the sepsis syndrome. We will review in depth various aspects of the major, central mediator, i.e., tissue necrosis factor (TNF)/cachectin, and also briefly discuss the interleukins IL-6 and IL-1.
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PMID:The role of cachectin/TNF and other cytokines in sepsis. 192 35

Cachectin/tumor necrosis factor (TNF-alpha) is a macrophage-secreted cytokine initially found to be a lipoprotein lipase-suppressing serum factor in cachectic, parasite-infected animals. Cloning of the cDNA encoding the gene for cachectin enabled biosynthesis of recombinant human cachectin and proof that the protein is identical to TNF-alpha. Numerous biological activities have subsequently been attributed to this pluripotent cytokine. In addition to suppressing LPL, cachectin/TNF mediates decreased lipogenic enzyme synthesis in adipocytes, causing a state of "cellular cachexia" in vitro. Similarly, catabolic cellular energy responses are induced by cachectin/TNF in cultured skeletal muscle cells which exhibit accelerated glycogenolysis, enhanced lactate production, and increased expression of hexose transporters. Persistent cachectin/TNF production occurs in chronic infection and malignancy, and chronic exposure induces a cachexia syndrome characterized by anorexia, weight loss, and anemia. Acute systemic appearance of cachectin/TNF is capable of inducing a state of lethal shock, disseminated hemorrhagic necrosis, catabolic hormone release, and multiple organ injury. Inhibiting the toxic effects of cachectin/TNF with monoclonal anti-cachectin antibodies during overwhelming Gram-negative bacteremia confers protection against septic shock. In these studies, the unprotected controls succumbed within hours, but baboons immunized against cachectin/TNF did not develop the characteristic increases of IL-1, IL-6, or catabolic stress hormones and did not die, suggesting that cachectin/TNF is a pivotal, proximal factor in the humoral cascade mediating septic shock syndrome. Recent evidence indicates that when produced in lesser quantities, cachectin/TNF may participate in the degradative and reparative mechanisms of physiological tissue remodelling and homeostasis. Future studies of the immunological and metabolic effects of cachectin/TNF should lead to a better understanding of the pathogenesis of infection and inflammation.
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PMID:Metabolic responses to cachectin/TNF. A brief review. 219 78

This study has evaluated the relationship between tumor growth and induction of acute-phase proteins. It has also determined whether an intact cellular immunity is obligatory for a fully expressed acute-phase plasma protein response in the presence of a highly antigenic tumor. Quantitatively, acute-phase responses (protein synthesis, plasma concentrations, hepatic RNA content, anorexia) were proportional to tumor burden. Anti-inflammatory drugs (indomethacin 1 micrograms/g body wt, dexamethasone 0.5 micrograms/g body wt) had no direct effect on the attenuation of the systemic acute-phase responses, but did affect them indirectly by decreasing tumor growth. Immune suppression (cyclosporine A at 20 or 60 micrograms/g body wt) had no effect on either acute-phase reactions or local tumor growth. In endotoxin-stimulated (lipopolysaccharide) normal mice, immune suppression aggravated anorexia and caused high mortality, while dexamethasone partly reversed these effects in endotoxin-stimulated mice. Plasma levels of acute-phase proteins correlated to circulating levels of IL-6 in untreated tumor-bearing mice, but this relationship was not obvious in either drug-treated tumor-bearing or endotoxin-stimulated mice. Tumor tissue induced the synthesis of different acute-phase proteins compared to endotoxin. However, disintegrated normal liver tissue induced the synthesis of serum amyloid protein to the same extent as the growing tumor. This effect was primarily associated with the mitochondrial/lysosomal and microsomal liver cell fractions. In conclusion, the overall acute-phase protein response is not a modulating factor of tumor growth.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute-phase proteins in response to tumor growth. 750 21

There is some evidence that major depression is characterized by systemic immune activation with involvement of phagocytic cells, T cell activation, B cell proliferation and increased autoantibody production. This paper reviews that major depression may be accompanied by higher concentrations of positive and lower concentrations of negative acute phase proteins (APPs). The most prominent abnormalities of APPs in major depression are increased haptoglobin (Hp) plasma levels. The latter are significantly and positively correlated with interleukin (IL)-6 production, various indices of systemic immune activation (e.g. monocytosis, neutrophilia, T cell activation) and with the vegetative symptoms of depression (e.g. anorexia, weight loss, psychomotor retardation, sleep disorders, anergy). Major depression is characterized by an altered distribution of Hp phenotypes and genes suggesting that genetic variation on chromosome 16 may be associated with this illness. It is concluded that increased production of IL-6 and IL-1 in major depression may underlie both immune activation and the "acute" phase response in that illness, and that disorders in Hp may be related to the pathophysiology and pathogenesis of major depression.
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PMID:A review on the acute phase response in major depression. 750 8

Some aspects of humoral and cell-mediated immunity and the capacity of peripheral blood mononuclear cells (PBMCs) of fourteen elderly persons with idiopathic anorexia to produce several cytokines, such as tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), interleukin-6 and interferon-gamma (IFN gamma), were studied and the results were compared with those obtained in a control group of ten age-matched, normal weight healthy subjects. In addition, spontaneous and induced production of these cytokines was also measured in cultures of PBMCs of fourteen healthy young individuals as a control group of age. A significant decrease in CD2 (pan T-cells) and CD4 (T-helper) lymphocyte subpopulations, but unchanged CD8 (T-suppressor) subset, and a reduced response in delayed cutaneous hypersensitivity tests were observed in senile underweight anorectic patients. Monocyte counts did not show significant differences between patients and control subjects. The spontaneous release by PBMCs of all the cytokines measured did not differ between the anorectic and either the elderly or young control group. A significant increase in IL-6 production after mitogen stimulation with tetradecanoylphorbol acetate (TPA) and phytohemagglutinin (PHA) after 24 and 48 h of culture, as well as a greater induced TNF alpha production after 48 h of incubation with the same mitogens, was found in the anorectic patients as compared with the elderly controls. However, stimulated production of both IL-1 beta with TPA and of IFN gamma with PHA did not differ significantly between anorectics and aged controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cell-mediated immune response and cytokine production in idiopathic senile anorexia. 773 Dec 74

The trauma of elective surgery leads to the release of cytokines, many of which act primarily at local level having been released from tissue macrophages, circulating monocytes or other activated tissues. There is also a reproducible response in plasma IL-6, the magnitude of which relates to the magnitude of operative trauma. It seems likely that cytokines have an important role in mediating the anorexia associated with the postoperative period, and this may be associated with increased release of CRF from the hypothalamus. Further studies on the interrelationship between cytokine and neuroendocrine systems will lead to a greater understanding of the control of food intake following injury, and will permit the development of new strategies to improve the effectiveness of nutrition at this time.
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PMID:Cytokine changes in the postoperative period. 802 25

Patients with advanced cancer and cachexia typically demonstrate modestly increased rates of energy expenditure in the presence of diminished food intake due to anorexia and to gastrointestinal disturbances. Rates of glucose production by the liver, gluconeogenesis and glycolysis to lactate (Cori cycle) are increased, fat mobilisation and oxidation are accelerated. There is a redistribution of body proteins away from muscle towards visceral proteins, resulting in marked muscle protein loss. Cancer cachexia differs from simple starvation and demonstrates metabolic similarities to sepsis or polytrauma. The metabolic response in the patient with cancer is largely due to mediators released by the tumour or by the host; recently the role of cytokines such as tumour necrosis factor alpha (TNF alpha), interleukin-1 (IL-1) and -6 (IL-6) and interferon gamma (INF gamma) has been emphasized. Catabolic hormones such as glucocorticoids and adrenaline have also been implicated. Cytokines have the potential to reproduce experimentally the clinical syndrome of cancer cachexia. There is evidence of increased production of several of them in certain types of cancer. There are overlapping activities of the cytokines TNF alpha, IL-1, IFN gamma and IL-6. The contribution of each of them to cancer cachexia remains unclear. Inhibition of cytokine activity using specific antibodies in cancer-bearing experimental animals demonstrated partial prevention of cachexia. A positive feedback between macrophage-derived IL-1 and tumour-derived IL-6 has been demonstrated recently in experimental cancer cachexia. Cytokines may support tumour growth by acting as growth factors.
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PMID:Pathophysiology of cancer cachexia. 815 43

The constitutive expression of tumor necrosis factor-alpha (TNF alpha) mRNA and its induction (60 min later) by peripheral injection of Escherichia coli lipopolysaccharide (2 mg/kg i.p.) was demonstrated by polymerase chain reaction (PCR), in the pituitary and hypothalamus but not in the striatum or hippocampus of the rat. The pattern of TNF alpha mRNA induction is different from that observed for mRNAs of IL-1 alpha and IL-1 beta, IL-1ra and IL-6 respectively. This demonstration of the induction of TNF alpha in the brain may contribute to our understanding of the central effects of TNF alpha in fever and anorexia.
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PMID:Induction of tumor necrosis factor-alpha mRNA in the brain after peripheral endotoxin treatment: comparison with interleukin-1 family and interleukin-6. 825 3


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