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)

A subclone (clone 20) of chemically induced, murine colon adenocarcinoma with a potent ability to induce cachexia and another subclone (clone 5) without such an activity were transplanted to syngeneic mice (CDF1) and their tissue weights, blood components and cytokine levels in sera were compared. Mice transplanted with clone 20 showed a profound body-weight loss by 15 days after inoculation when the tumor accounted for less than 1% of the body weight, along with marked reduction of food and water intakes. Thereafter, they transiently gained in body weight with restoration of food and water intakes. Thus, the change in body weight was biphasic and not proportional to the tumor size. Body fat was lost preferentially, accompanied with a decrease in plasma triglyceride levels. The thymus contracted remarkably, and the peripheral lymphocyte count decreased extensively. Mice transplanted with clone 5, in contrast, did not show any of these changes characteristic of cachexia. Serum concentration of interleukin-6, which has been proposed as the principal inducer of cachexia in mice with colon 26, increased in mice with clone 5 to levels comparable to those in mice with clone 20. The changes in mice bearing clone 20 could not all be explained in terms of known biological activities of interleukin-6. Additional unknown factors, therefore, are presumed to contribute to cachexia in mice with clone 20. Identification of them should be helpful in the care of cachectic patients.
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PMID:Characterization of mice bearing subclones of colon 26 adenocarcinoma disqualifies interleukin-6 as the sole inducer of cachexia. 782 97

Johne's disease is characterized by a chronic enteritis that results in granulomatous inflammation, cachexia, and eventual death of cattle infected with Mycobacterium paratuberculosis. The cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6) have been associated with granuloma formation and wasting in other disease syndromes. The potential role of these cytokines in the development and progression of Johne's disease has not been investigated. Freshly isolated bovine peripheral blood monocytes and the murine macrophage cell line RAW 264.7 were examined for their ability to release inflammatory cytokines in response to mycobacterial cell wall components. Bovine monocytes and RAW 264.7 cells incubated with M. paratuberculosis lipoarabinomannan (LAM), muramyl dipeptide (MDP), or lipopolysaccharide (LPS) released TNF-alpha, IL-1 beta, and IL-6 as detected by appropriate bioassays. Using the RAW 264.7 cells, cytokine mRNA levels were elevated after in vitro incubation with live M. paratuberculosis or LPS as determined using a reverse-transcriptase polymerase chain reaction procedure.
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PMID:Mycobacterial cell wall components induce the production of TNF-alpha, IL-1, and IL-6 by bovine monocytes and the murine macrophage cell line RAW 264.7. 783 May 27

The clinical syndrome of cachexia is characterized by anorexia, continued losses of lean body mass, and altered carbohydrate and lipid metabolism. As early as the 1930s, this "chronic wasting" syndrome had been identified as the most frequent immediate cause of death in patients with cancer [Warren: Am J Med Sci 184:610-619, 1932]. At present, controversy remains as to the benefit of supplemental parenteral or enteral feedings in the nutritional repletion of cachectic cancer patients, since only selected patient groups have demonstrated clear benefit from their administration [Copeland et al.: Cancer 43:2108-2116, 1979; Copeland et al.: Cancer Res 37:2451-2456, 1977; Terepka and Waterhouse: Am J Med 20:225-238, 1956]. Despite having these advanced nutritional modalities firmly in our therapeutic armamentarium, the progression of cachexia in the nutritionally depleted cancer patient often continues unabated, and our ability to intervene successfully remains limited. This review proposes that host: tumor interactions lead to a nonspecific inflammatory response mediated in part by the chronic production and release of proinflammatory cytokines, including interleukin-1, tumor necrosis factor alpha, interleukin-6 and interferon-gamma, which antagonize the anabolic signals associated with enteral and parenteral nutrition support. Cytokine-mediated alterations can explain the inability of adequate dietary nitrogen and calories to result in lean tissue repletion. Based on this proposal, interrupting proinflammatory cytokine production or target organ action may be an appropriate therapeutic objective to improve nutrient utilization in patients with tumors.
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PMID:Cytokine-mediated alterations in host metabolism prevent nutritional repletion in cachectic cancer patients. 784 87

Humoral hypercalcemia of malignancy is a paraneoplastic syndrome believed to be due to production by the tumor of substances that stimulate osteoclastic bone resorption primarily. The human renal cell carcinoma cell line RC-8, grown in nude mice, was investigated for factors involved in renal cancer-induced hypercalcemia. At a tumor load of 200 to 400 mm.3 the mice developed hypercalcemia and hypophosphatemia associated with a rise in serum 1,25-dihydroxyvitamin D concentration and cachexia. The tumor released 1) significant amounts of human interleukin-6 (IL-6) and 2) parathyroid hormone-related peptide (PTHrP) into the circulation. Cancer cells further expressed mRNA for both human IL-6 and PTHrP. No secretion of human tumor necrosis factor-alpha or interleukin-1 beta could be demonstrated in the circulation of the host. Antibodies to IL-6 caused a significant (p = 0.043) inhibition of tumor growth and decreased serum calcium concentrations compared with control animals. Our data suggest that IL-6 is involved, either directly or indirectly, in the development of hypercalcemia in renal cell carcinoma.
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PMID:Hypercalcemia and cosecretion of interleukin-6 and parathyroid hormone related peptide by a human renal cell carcinoma implanted into nude mice. 786 50

Anorexia, net proteolysis of skeletal muscle and consumption of body fat are hallmarks of the cachexia syndrome associated with chronic disease states. While inanition contributes to cachexia, this wasting diathesis has little in common with simple starvation. The cachexia syndrome is characterized by progressive weight loss and depletion of lean body mass in excess to that resulting from comparable caloric restriction. Accelerated mobilization and consumption of host protein stores from peripheral tissues occurs to support gluconeogenesis and acute phase protein synthesis [1, 2]. In contrast, simple starvation is associated with a relative sparing of lean tissue with the preferential consumption of fat. While the clinical manifestations of cachexia are readily apparent, identification of the specific mechanisms responsible for the development of cachexia remains an enigma. In recent years, interest has focused on the role that the immune system plays in the development of cachexia. Investigators initially hypothesized that the chronic production of two inflammatory cytokines, tumour necrosis factor alpha (TNF alpha) and/or interleukin-1 (IL-1), could explain the host non-specific responses resulting in cachexia [3-5]. Other pro-inflammatory cytokines, including interleukin-6 (IL-6) [6, 7] and interferon-gamma [8, 9], have been more recently proposed to be involved in this complex process. Although no consensus exists for the exclusive role of any one cytokine in the pathogenesis of cachexia, there is growing acceptance that the progression of cachexia results in part from the inappropriate release of one or more pro-inflammatory cytokines [10, 11]. In the present review, the current role of TNF alpha as a mediator of cachexia is examined.
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PMID:Tumor necrosis factor and cachexia: a current perspective. 788 18

We studied the biological features of cacheixa using renal cell carcinoma heterotransplanted to nude mice (JRC 11) where cachexia was caused after the inoculation of tumour. The results of our study were as follows; 1) The JRC 11 tumour expressed mRNA of interleukin-6 by the analysis using the polymerase chain reaction method (PCR). 2) The human IL-6 was detected in the sera of nude mice according to the growth of JRC 11. On the other hand, human IL-1-beta, human tumour necrosis factor (hTNF)-alpha and human interferon (hIFN)-gamma were not detected. 3) The serial body weight of nude mice excluding tumour weight decreased at the 3rd week after the inoculation of tumour compared with tumour non-inoculated mice (control). Furthermore, the experimental group performed the resection of JRC 11 at the 3rd week after the inoculation of tumour showed a re-increase in the body weight, and reached the same weight as that of the control group at the 6th week after the inoculation of tumour. At the same time, serum hIL-6 was not detected in this group. 4) The serial weight of visceral organs including the liver, kidney and spleen began to decrease at the 3rd week after the inoculation of tumour compared with the control group. We conclude that serum IL-6 is defined as a promoter of cachexia in renal cell carcinoma relating to paraneoplastic syndrome.
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PMID:[A study on the relationship between the production of cytokines and the biological features of cachexia using renal cell carcinoma heterotransplanted to nude mice]. 789 29

Increased interleukin-6 (IL-6) production and expression by malignant cells of the IL-6 receptor has been evidenced in a subgroup of non-Hodgkin's lymphomas, suggesting that this cytokine plays a role in lymphoma growth and in B clinical symptoms. In this study, the effect of the administration of an anti-IL-6 monoclonal antibody (MoAb) was analyzed in 11 patients seropositive for human immunodeficiency virus-1 and suffering from an immunoblastic or a polymorphic large-cell lymphoma. The antibody (BE-8, 10 to 40 mg/day) was administered for 21 days. Neutralization of in vivo IL-6 effect was assessed by monitoring C-reactive protein levels in the serum. In 5 patients, the lymphoma progressed during treatment. Among them were the 2 patients in whom endogenous IL-6 effect was not neutralized. Five patients experienced a stabilization, and 1 a partial remission. This effect on lymphoma growth lasted for 8 to 28 weeks. The anti-IL-6 MoAb had a clear effect on lymphoma-associated fever and cachexia. The mean body weight increase was 1.4 +/- 0.5 kg between day 1 and day 21, and reached 12 kg in 120 days in 1 patient who received three courses of treatment. Side effects were a consistent but moderate thrombocytopenia, and an occasional and moderate decrease of neutrophil counts. Immunization against the MoAb was observed in only 2 patients. These results indicate that in some cases of lymphomas growth of malignant cells may be partially IL-6-dependent and that neutralizing endogenous effect of IL-6 completely abrogates B clinical symptoms.
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PMID:Administration of an anti-interleukin-6 monoclonal antibody to patients with acquired immunodeficiency syndrome and lymphoma: effect on lymphoma growth and on B clinical symptoms. 791 67

Intranasal administration of an inoculum of 10(7) focus-forming units (FFU) of respiratory syncytial (RS) virus induced disease in BALB/c mice with signs of anorexia, cachexia, ruffled fur, and pneumonia. Mice displayed mild signs of illness on day 1 postinoculation (PI), followed by a transient recovery phase of 3 days. Disease rapidly reappeared on day 5 PI and worsened on subsequent days, with mortalities by day 7 PI. Mice inoculated with 5 x 10(6) FFU exhibited milder signs of disease, while those inoculated with 2 x 10(6) FFU and control mice given only Hep-2c cell suspension exhibited no noticeable signs of illness. High levels of bioactive tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were detected in both lungs and sera of mice inoculated with 10(7) FFU of virus. Peak levels of both cytokines were detected at day 1 PI but remained detectable throughout the 7 day period studied postinoculation. Cytokine levels were much lower or were undetectable in control mice. These results suggest that the macrophage is stimulated in vivo to produce inflammatory cytokines in response to RS virus infection.
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PMID:In vivo production of tumour necrosis factor-alpha and interleukin-6 in BALB/c mice inoculated intranasally with a high dose of respiratory syncytial virus. 804 22

We established a cancer cachexia model in BALB/c mice bearing Colon 26 and examined antitumor and anticachectic activity of UFT. The mice bearing Colon 26 showed a progressive loss of body weight, loss of lipid, and hypalbuminosis associated with the change of tumor size and these symptoms were improved by removal of cancer. In this model UFT extended life span significantly at 15mg/kg/day though showed a little growth inhibitory activity. UFT showed a significant tumor growth inhibitory activity and extended life span at 20mg/kg/day and could reverse all biological parameters mentioned above. Since the intratumor and plasma contents of IL-6 were significantly lowered in the UFT administered group, it is estimated that the anticachectic activity of UFT originates from reduction of interleukin-6 in tumor.
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PMID:[Antitumor and anticachectic activity of UFT in BALB/c mice bearing colon 26 adenocarcinoma]. 808 52

Neoplastic diseases are frequently associated with metabolic changes collectively known as cancer cachexia. The presence of cachexia complicates therapeutic intervention and is an important cause of death in cancer patients. At present there is no effective treatment for cachexia. Recently, the involvement of interleukin-6 (IL-6) in the wasting of colon-26 adenocarcinoma-bearing mice was demonstrated. The research presented here establishes an anticachectic role for the experimental drug suramin, since it partially blocks (up to 60%) the catabolic effects associated with the growth of this tumor in vivo. Suramin prevents the binding of IL-6 to its cell surface receptor subunits, as demonstrated by radioreceptor binding assay and affinity crosslinking experiments. Furthermore, the uptake of radioactive IL-6 by the liver is significantly reduced in suramin-treated mice. On the other hand, the drug is approximately 10-fold less potent in inhibiting the binding of tumor necrosis factor-alpha to indicator cell line in vitro and fails to block liver uptake of this cytokine in vivo. Collectively, these results suggest that suramin inhibits cancer-associated wasting, in part by interfering with the binding of IL-6 to its receptor. Whether suramin inhibits the action of other factors/cytokines that may also participate in colon-26-mediated cachexia is not yet known.
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PMID:Suramin interferes with interleukin-6 receptor binding in vitro and inhibits colon-26-mediated experimental cancer cachexia in vivo. 822 30


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