Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0235394 (wasting)
 8,040 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism by which cord factor (CF), a toxic glycolipid from mycobacteria, induces cachexia was studied in BALB/c mice. Body weight was markedly reduced 48 h after CF administration; the animals became severely wasted and exhibited hypertriglyceridemia, hypoglycemia, and high levels of tumor necrosis factor (TNF) in plasma. After CF administration, a transferable factor which caused cachexia and hypertriglyceridemia in recipient mice was detected in the blood. Dexamethasone partially inhibited the cachexia-inducing action of CF. Conditioned medium from adherent peritoneal cell cultures incubated with CF produced the same wasting symptoms when inoculated intravenously into mice. These studies also demonstrated that adherent peritoneal cells produced a humoral factor in response to CF which was related to CF-induced cachexia. Antiserum to recombinant TNF-alpha prevented the cachectin action in passive-transfer experiments. Our findings indicate that cachectin (TNF) plays a role as a central mediator of the wasting induced by CF.
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PMID:Tumor necrosis factor (cachectin) mediates induction of cachexia by cord factor from mycobacteria. 305 51

TNF-alpha enhances HIV-1 replication in acutely and chronically infected cells and likely contributes to the wasting associated with the acquired immunodeficiency syndrome. Agents that inhibit TNF-alpha activity should theoretically delay the progression of disease, and several are currently in clinical trials. We hypothesized that IL-10, a cytokine that suppresses the gene expression and synthesis of TNF-alpha in monocytic cells, might inhibit HIV-1 replication. As expected, IL-10 suppressed PMA-induced TNF-alpha production in U1 cells; however, when U1 cells were cultured in the presence of PMA and increasing doses of IL-10, a dose-dependent increase in HIV-1 expression was observed. IL-10 also enhanced IL-1 beta-, TNF-alpha-, and GM-CSF-induced HIV-1 expression in U1 cells, and this occurred, at least in part, at the level of transcription. We next stimulated cells under conditions of TNF-alpha blockade. When PMA-induced TNF-alpha activity and HIV-1 replication were blocked by the presence of soluble TNF receptors, IL-10 independently enhanced HIV-1 replication. In contrast, other agents that are capable of blocking TNF-alpha synthesis or TNF-alpha activity either had no effect (IL-13 and IL-4) or inhibited HIV-1 expression (soluble TNF receptors and pentoxifylline) in U1 cells. These data suggest that IL-10, while inhibiting TNF-alpha synthesis, has an independent mechanism of action that enhances HIV-1 replication. Therefore, IL-10 may have undesirable effects in HIV-1-infected patients.
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PMID:Interleukin-10 enhances human immunodeficiency virus type 1 expression in a chronically infected promonocytic cell line (U1) by a tumor necrosis factor alpha-independent mechanism. 755 27

The present study aimed to determine plasma lipid levels in 95 HIV-infected patients divided into four groups according to the CD4 lymphocyte counts comparatively to a control group of 20 HIV-negative normolipidaemic subjects. A relationship between lipidic abnormalities and immune or nutritional status was also investigated. The patients below 200 CD4 lymphocyte mm-3 (groups 1 and 2) had significantly lower total cholesterol than the controls. The patients below 400 CD4 lymphocytes mm-3 (groups 1, 2, 3) had significantly higher triglycerides and Lp(a) but lower LDL-cholesterol than the controls. In all HIV-positive patients, whatever their CD4 lymphocyte count, HDL-C and apoA1 were lower than in the controls. By multivariate analysis triglycerides were positively correlated to acute opportunistic infections and to interferon-alpha levels, while cholesterol was negatively correlated to TNF-alpha, and LDL-C was positively correlated to albuminaemia. The latter parameter was the only lipidic value to correlate with nutritional markers. The contamination route, or the presence of wasting, was not correlated to any lipidic disorder.
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PMID:Plasma lipids in HIV-infected patients: a prospective study in 95 patients. 795 95

The cancer cachexia syndrome may be present in up to 80% of patients with cancer. Malnutrition resulting from cancer cachexia is a significant cause of morbidity and mortality. Anorexia, tissue wasting, and weight loss appear to be the result of metabolic abnormalities caused by host cytokine production in response to the tumor. The host cytokines include TNF-alpha, IL-1, IL-6, IFN-gamma, and D-factor. Nutritional support in the patient with cancer has been controversial, with the belief that tumor growth may be augmented; however, human studies fail to confirm that tumor growth occurs in excess of normal tissue growth. The efficacy of nutritional support in the cancer has not been adequately studied. Considerable interest exists in providing nutritional support pharmacologically to modify the response to malignancy.
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PMID:Cachexia and anorexia in malignancy. 881 1

BALB/c male mice acutely infected with Trypanosoma cruzi underwent a severe weight loss (around 20%, from day 18 to 31 post-infection), when compared to age-matched uninfected animals. Though mice regained weight later, when blood parasites were hardly detectable, wasting extended over the chronic phase of infection. The onset and the magnitude of weight loss were related to the mouse susceptibility to infection, since they were respectively earlier and higher in male mice which will die than in surviving ones, in males than in females, and in BALB/c than in B6D2 [(C57B1/6 x DBA/2)F1], a mouse strain more resistant to infection. Fat weight of infected mice (male BALB/c) was reduced by 60 to 80%, whereas lean mass was unaffected and water content rose by 6 to 10% in acute and chronic infection. Haematocrit was also decreased by 15-16% in acute infection. Animals failed to compensate their energetic loss since their food intake remained similar to that of uninfected animals. Injections of neutralizing anti-TNF-alpha monoclonal antibody into infected male mice, during the first two weeks but not later in infection, significantly attenuated the weight loss. Early administration of anti-IL-6 or anti-IFN-gamma MoAbs did not improve the mouse wasting. Taken together, these data show that TNF is a key agent of cachexia occurring in the acute T. cruzi infection in mice.
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PMID:The cachexia associated with Trypanosoma cruzi acute infection in mice is attenuated by anti-TNF-alpha, but not by anti-IL-6 or anti-IFN-gamma antibodies. 881 2

Peripheral blood mononuclear cells from HIV infected individuals develop in vitro apoptosis to a much higher extent than healthy donors. Aside from the direct cytopathic effect of HIV, programmed cell death can be induced by such cytokine system imbalance as seen with increased levels of TNF-alpha or the Th1-->Th2-cytokine shift. However, wasting syndrome, which occurs in the majority of AIDS patients is associated with an enhanced expression of TNF-alpha and IL 6 as well. A 37-year-old AIDS patient suffering from wasting syndrome and hypogonadism was treated with 1 alpha-dihydrotestosterone. The rate of apoptotic peripheral blood mononuclear cells was determined before, during and after this therapy. After three weeks of androgen substitution therapy, the rate of spontaneous apoptosis was reduced to 34% and the ionomycin induced apoptosis to 52% of the rate of apoptotic cells at the beginning of the therapy. Moreover, the general and nutritional condition improved remarkably. Thus, we suggest that the use of anabolic drugs for the treatment of AIDS-associated wasting-syndrome would not only improve their general and nutritional condition, but might also prevent the loss of CD4+ T-cells through an inhibition of apoptosis.
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PMID:Substitution of testosterone in a HIV-1 positive patient with hypogonadism and Wasting-syndrome led to a reduced rate of apoptosis. 904 91

The pathogenesis of protein wasting in chronic renal failure is multifactorial. Potential mediators of protein catabolism in chronic uremia include anorexia, low protein-energy intake, increased cortisol and parathyroid hormone secretion, insulin resistance, metabolic acidosis and unidentified uremic toxins. In non-acidotic uremic patients the rate of protein turnover (that is, synthesis and degradation) has often been found to be decreased. Malnutrition also decreases both protein synthesis and degradation. In contrast, during acidosis protein degradation is primarily accelerated and results in rapid loss of body proteins. Cytokine concentrations have often been found increased in both dialyzed and undialyzed chronically uremic patients. Our study determined the circulating levels of TNF-alpha and of type I (60 kDa) and type II (80 kDa) soluble TNF-alpha receptors in undialyzed uremic patients, and found that their plasma levels were greatly increased. Serum creatinine correlated with TNF-alpha soluble receptors but not with the TNF-alpha. Thus, TNF-alpha is potentially an important mediator of protein wasting in chronically uremic patients. Pharmacological therapy of protein catabolism in chronic uremia may include the administration of pentoxifylline, which has been shown to decrease protein degradation by interfering with the TNF-alpha system (that is, TNF-alpha and its soluble receptors) in experimental models. Growth hormone and insulin-like growth factor-1 administration may also be beneficial in these patients, but further evaluation of the hormone effects on glucose and glutamine metabolism is called for.
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PMID:Mechanisms of malnutrition in uremia. 935 Jun 78

Cachexia consists of a constellation of metabolic changes that occur in cancer patients, including the reduction of muscle and fat tissue, asthenia, anorexia, hypoglycemia and hypercalcemia. These syndromes complicate therapeutic intervention and decrease the quality of life of the patient. This review discusses the involvement of cytokines in cancer cachexia and describes the contribution of IL-6 and other cytokines to the wasting of C-26-bearing mice. The neutralization of IL-6 by antibody, or IL-6 receptor antagonism by suramin, significantly reduce the severity of key parameters of cachexia. The participation of several other factors (PGE2, IL-1, IL-10 and TNF-alpha) in the cellular communication between the C-26 tumor cell and tumor-infiltrating macrophages is also described.
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PMID:Inhibition of experimental cancer cachexia by anti-cytokine and anti-cytokine-receptor therapy. 938 67

The toxic oil syndrome (TOS) was caused by the ingestion of an adulterated rapeseed oil containing oleic acid anilide (OAA). It was characterized by lethal symptoms in the acute phase and by symptoms of idiopathic autoimmune diseases in the chronic phase. The pathogenetic mechanisms remain unclear. In a murine model of TOS we demonstrate strain-dependent effects on the immune system after treatment with OAA intraperitoneally. While C57BL/6 (H-2b) mice develop a polyclonal B cell activation without disease symptoms, most A/J (H-2a) mice suffer an acute lethal wasting disease. These differences are reflected in the splenic cytokine gene expression and secretion and in the Ig production. Increased IgE serum levels and reduced TNF-beta mRNA suggest a Th2 cell response in C57BL/6 mice. In A/J mice, splenocytes express IL-1alpha, IL-10, and IFN-gamma mRNA in vivo and secrete high levels of TNF-alpha in vitro. These observations resemble the human condition in TOS with development of either an acute lethal disease or a chronic autoimmune-like disease. As in other chemical-induced reactions genetic susceptibility seems to be important.
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PMID:Strain-dependent cytokine profile and susceptibility to oleic acid anilide in a murine model of the toxic oil syndrome. 947 29

The requirements for interleukin (IL)-12/signal transducer and activator of transcription (Stat)-4 signaling and induction of T cell-specific interferon (IFN)-gamma expression in the development of T helper cell (Th)1-type pathology were examined in two different models of experimental colitis. In each model, abnormal reconstitution of the T cell compartment in immunodeficient mice by adoptive cell transfer leads to a wasting syndrome and inflammation of the colon, induced by IFN-gamma and tumor necrosis factor (TNF)-alpha-producing T cells. We show here that treatment with anti-IL-12 antibodies in one of the models, or reconstitution with T cells from Stat-4-deficient (Stat-4(null)) mice in both models resulted in a milder disease in the majority of recipient animals, compared with those that were left untreated or that had been reconstituted with wt cells. Protected mice in each group also harbored lower frequencies of IFN-gamma-producing T cells than did diseased mice, suggesting that effects on wasting and colitis resulted from the attenuation of IFN-gamma expression by T cells. To test whether the development of pathogenic T cells in the two colitis models was directly dependent on T cell-specific IFN-gamma expression, IFN-gammanull donors were used for T cell reconstitution in each system. Surprisingly, large numbers of IFN-gammanull-reconstituted mice developed wasting and colitis, which in many cases was of comparable severity to that seen in animals reconstituted with wt cells. Furthermore, T cells from these animals expressed TNF-alpha, demonstrating that they had retained the ability to produce another proinflammatory cytokine. Taken together, these results demonstrate that in some forms of chronic experimental colitis the development of pathogenic T cells is influenced predominantly, though not exclusively, by IL-12 via the actions of Stat-4 proteins. Furthermore, our data suggest that in the models of colitis studied here the effects of IL-12/Stat-4 or other Th1 promoting pathways are not limited to the induction of IFN-gamma gene expression in T lymphocytes.
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PMID:T cell-mediated pathology in two models of experimental colitis depends predominantly on the interleukin 12/Signal transducer and activator of transcription (Stat)-4 pathway, but is not conditional on interferon gamma expression by T cells. 954 34


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