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

It has been suggested that, as part of the inflammatory response to the presence of a tumor, various cytokines are produced and these induce hepatic synthesis of acute-phase proteins (APP). Under these circumstances it is not known what changes occur in the fixed component of hepatic protein synthesis. The aim of this study was to compare circulating interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF) concentrations and fixed hepatic protein synthesis rates in a group of healthy controls (n = 6) with a group of patients with an established APP response secondary to hepatic metastasis from colorectal cancer (n = 6). Fixed hepatic protein synthesis rates were measured following a primed, constant 20-hour infusion of 15N-glycine. The liver was biopsied at laparotomy. The APP response was assessed by serum C-reactive protein concentration and cytokines were assayed by a combination of immunoassay and bioassay. The patients with advanced cancer and an on-going APP response had elevated circulating IL-6 concentrations (p less than 0.01). Rates of fixed hepatic protein synthesis were 30% lower than those observed in controls (p less than 0.01). These findings demonstrate that in patients with hepatic metastasis, although the synthesis of certain acute-phase export proteins can be increased, fixed protein synthesis is reduced. Whether these changes in the distribution of hepatic protein synthesis are mediated by IL-6 will require further investigation.
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PMID:Elevated circulating interleukin-6 is associated with an acute-phase response but reduced fixed hepatic protein synthesis in patients with cancer. 189 91

Phagocytosis is the process where specific cells, phagocytes, ingest foreign material, include it in a cytoplasmatic vacuole, called phagosome, and destroy it. The function of phagocytosis in the immune response has been underevaluated for a very long time. Phagocytosis however, appears to be more and more important in our defense against infection and cancer. The uremic patient presents a well known and increased tendency for infectious disease as well as an increased incidence of cancer. Modern methodology for investigation of phagocytic function consists of: 1. measuring the respiratory burst during phagocytosis; by examining the radio-active CO2 production during the glucose metabolization of phagocytosis. 2. During the chemical reaction of the respiratory burst light is produced. This chemiluminescence can be measured in a Lumetron. In uremia the registration of that chemiluminescence can however be disturbed by the presence of uremic toxins, acting as scavengers of free radicals. 3. Measurement of interleukin-1, interleukin-6 or tumor necrosis factor production during phagocytosis. In the present study, we investigated glucose metabolization and radioactive CO2 production without stimulation and after a challenge with Latex, Zymosan or Staphylococcus Aureus. All tests have been performed on 50 microliter whole blood samples. The following uremic situations have been investigated: 1. Several degrees of increasing renal failure. 2. First weeks of hemodialysis maintenance treatment. 3. Hemodialysis session. 4. Course of hemodialysis maintenance treatment. 5. Continuous ambulatory peritoneal dialysis (CAPD) and renal transplantation. 6. Changes after chemical stimulation by a cephalosporin (cefodizime (R)). The Authors report their detailed results of these investigations and conclude as follows: --uremia is a prototype of acquired immune deficiency. --Contact with bio-incompatible membranes during hemodialysis is disastrous for phagocytosis. --Other toxins than the classical urea or creatinine are apparently responsible for the phagocytic disturbances. --Stimulations of phagocytosis with medication such as the cephalosporin, Cefodizime(R) (Hoechst) is possible.
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PMID:[Phagocyte function in uremic patients]. 192 26

A number of human hematopoietic growth factors have been genetically cloned and recombinant proteins produced. Several phase I and II clinical trials have already been published and results from phase III studies are becoming available. The use of erythropoietin to alleviate chemotherapy-induced myelosuppression is being tested. Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor have been extensively studied in patients receiving chemotherapy at standard or escalated doses and after bone marrow transplantation and appear to ameliorate chemotherapy-induced neutropenia and to speed bone marrow engraftment after high-dose cancer therapy. Interleukin-3 and interleukin-6 are quite early in their clinical development, but appear able to alleviate post-chemotherapy thrombocytopenia.
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PMID:Hematopoietic growth factors as supportive therapy for cancer- and chemotherapy-induced conditions. 193 23

Concentrations of interleukin-6 and neopterin were measured in sera from 44 patients with multiple myeloma. To judge the relative prognostic value of these analyses, other clinical and laboratory variables were concomitantly determined. The patients were followed up to 9 years, and the abilities of all variables to predict outcome were assessed. Both neopterin (P = 0.0008) and interleukin-6 (P = 0.033) were significantly higher in patients with higher stages of the disease. The correlation between interleukin-6 and neopterin was weak but significant (Spearman's rank correlation coefficient, 0.38; P = 0.019). By univariate survival analysis using the product-limit approach, both neopterin (P = 0.0001) and interleukin-6 (P = 0.025) were identified as significant predictors of survival. Multivariate survival analyses by the proportional hazards technique demonstrated that either stage and neopterin or neopterin and interleukin-6 are useful combinations of predictor variables. Thus, interleukin-6, which is supposed to influence progression of multiple myeloma in an autocrine or paracrine manner, failed to contribute to prediction if stage was included in a model. In contrast, neopterin remained significant in all multivariate models.
Cancer Res 1991 Dec 01
PMID:Predictive value of interleukin-6 and neopterin in patients with multiple myeloma. 193 85

We have treated 17 patients with 5-fluorouracil (5-FU, 300 mg/m2/d by continuous ambulatory infusion for 8 weeks) and interferon alfa-2b (escalating doses to cohorts of three to five patients, given subcutaneously on a daily schedule at 2.0, 3.5, 5.0, and 10.0 x 10(6) IU/m2). The two major toxicities observed were mucositis, which occurred in 10 patients at 2 weeks and required interruption of therapy and 5-FU dose reduction, and chronic fatigue syndrome, which required reduction of the dose of interferon alfa-2b. Other toxicities seen included elevation in BUN/creatinine, elevation in liver function tests, alopecia, diarrhea, confusion, and myelosuppression. No toxic deaths occurred. Five responses were observed: two complete responses, two partial responses, and one minor response, all in patients with gastrointestinal malignancy; three of the responding patients had previously failed 5-FU-containing regimens. When we measured 5-FU plasma levels in nine of our patients, they were at or below 1 ng/mL in most patients; however, within 1 hour of administration of interferon alfa-2b, plasma levels rose 16-fold. This elevation of 5-FU levels persisted for at least 24 hours, and could not be accounted for on the basis of altered interleukin-6 levels. When the regimen was tested in eight patients with metastatic renal cell carcinoma as part of a pilot study, three partial responses were observed, and no patient developed disease progression while on treatment. The combination of 5-FU, given by continuous infusion, and interferon alfa-2b, given daily, appears worthy of advancement to phase II trials.
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PMID:alpha-Interferon and 5-fluorouracil: possible mechanisms of antitumor action. 194 33

The biologic in vivo effects of recombinant human interleukin-3 (rhIL-3) were assessed in a phase I clinical study of 30 patients with advanced malignancy. On day 1 rhIL-3 was administered by a single intravenous (IV) bolus injection, followed by subcutaneous (SC) injections once daily from day 2 to 15; at least three patients were treated at each dose level (60, 125, 250, and 500 micrograms/m2). A transient decrease of eosinophil and monocyte counts was observed immediately after IV injection of rhIL-3, whereas the neutrophil count remained unaffected. Total WBC counts and neutrophil counts increased dose dependently up to threefold, whereas a 10-fold to 50-fold rise was observed in levels of circulating eosinophils and basophils. Platelet counts increased up to twofold. Patients developed moderate increases of serum levels of soluble interleukin-2 receptors, beta 2-microglobin, and immunoglobulin M (IgM), and of the acute phase reactants, C-reactive protein (CRP), fibrinogen, and haptoglobin. An increase in interleukin-6 (IL-6) serum levels was detected in patients treated by IV bolus rhIL-3. The serum half-life of IV injected rhIL-3 was 20 +/- 3 minutes; after SC administration, 210 +/- 15 minutes. Administration of rhIL-3 was generally well tolerated, with mild fever, headache, and local reactions at the injection site being the most frequent side effects. The primary course of the underlying malignant diseases was not significantly altered by administration of rhIL-3. The results indicate that rhIL-3 acts in vivo as a multilineage hematopoietic growth factor and a weak inflammatory mediator that may be used successfully to improve states of hematopoietic failure.
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PMID:Biologic effects of recombinant human interleukin-3 in vivo. 196 May 53

Recent studies have suggested that intestinal epithelial cells demonstrate some of the functions associated with immune competent cells. Based on these observations, we investigated whether gastrointestinal epithelial cells express Interleukin-6 (IL-6). The presence of this cytokine was tested in 53 normal and pathological tissue specimens of the human gastrointestinal tract using an immunohistochemical technique with anti-IL-6 monoclonal and polyclonal antibodies. Immunostaining shows that IL-6 is expressed in gastric and small intestinal epithelial cells. The tumor cells from a large subset (11 of 15) of colon cancer specimens were strongly immunostained. IL-6 immunostaining was less conspicuous and less frequent in the epithelial cells of normal colonic mucosa. Northern blot experiments indicated that the expression of IL-6 in colonic mucosa correlates quantitatively with the presence of its m-RNA. Furthermore, IL-6 receptor (IL-6R) m-RNA was also detected and was twice as abundant in colonic carcinoma as in normal colon. It is concluded that mucosal epithelial cells of the gastrointestinal system express IL-6 and that in the case of the colon, malignancy is accompanied by a higher expression. In addition, the presence of IL-6R transcript suggests that normal and neoplastic colonic epithelial cells might be autocrinally regulated by IL-6.
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PMID:Interleukin-6 and its receptor are expressed in human intestinal epithelial cells. 197 Jun 94

Renal cell carcinoma cells produced the substance(s) which killed them (suicide factor(s)) after co-culture with mumps virus. The suicide factor(s) were heat-sensitive and were degraded with trypsin. Furthermore, actinomycin D inhibited the production of the substance(s) by cancer cells. Considering these facts, the substance(s) were thought to be protein(s) derived from de novo synthesis in cancer cells. It was demonstrated that renal cell carcinoma cells proliferated with the autocrine loop of interleukin-6 (IL-6). Mumps virus almost completely inhibited the IL-6 production in several hours. Because of these two facts, the suicide process might be initiated in renal cell carcinoma cells after encountering mumps virus, i.e. inhibition of the autocrine growth loop of IL-6 followed by the induction of an autocrine killing loop of unknown substance(s).
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PMID:Suicide process of renal cell carcinoma cells encountering mumps virus. 199 9

The human leukemic cell line AML-193 was tested for its proliferative response to endogenously produced autocrine factors and to a variety of cytokines and colony-stimulating factors. Cells grown in the absence of GM-CSF incorporated tritiated thymidine, and this was partially reversed by adding neutralizing anti-GM-CSF antibodies to the culture medium, suggesting that it was due, at least in part, to autocrine GM-CSF production. This was confirmed by immunopurification of a GM-CSF-like activity from cell supernatant of AML-193 cells grown in serum free medium in the absence of exogenous GM-CSF. When AML-193 cells were cultured with GM-CSF in combination with other cytokines, Interleukin-1 alpha and beta (IL-1 alpha and beta), Interleukin-3 (IL-3), Interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF) and tumor necrosis factor alpha (TNF alpha), none of them affected the concentration of GM-CSF required to induce 50% of maximum proliferation (D50). However, the maximum proliferation induced by GM-CSF alone was drastically decreased by IL-1 alpha, IL-1 beta and TNF alpha. Inhibition caused by exposure of the AML-193 to IL-1 for up to 24 hr was reversible, ruling out a direct cytotoxic effect.
Int J Cancer 1991 Feb 01
PMID:Growth regulation of the AML-193 leukemic cell line: evidence for autocrine production of granulocyte-macrophage colony-stimulating factor (GM-CSF), and inhibition of GM-CSF-dependent cell proliferation by interleukin-1 (IL-1) and tumor necrosis factor (TNF alpha). 199 54

The prediction of tumour biology rarely rests upon a single characteristic of the malignancy. The analysis of a single gene can complement standard histologic evaluation. The investigation of new parameters as well as the routine clinical analysis of gene expression is often limited because of the small amount of tissue available. This is particularly true of de novo human bladder cancers because they are generally small or handled in such a way as to hinder the analysis of multiple different parameters. Analysis of expressed mRNA by the polymerase chain reaction (RNA/PCR) is a method that allows the development of a profile of bladder cancer gene expression. The authors report the use of the RNA/PCR method to examine in bladder cancer the expression of the human leukocyte antigen (HLA) class II gene family (HLA-DR, DQ, and DP) as well as interleukin-6 (IL-6) and the interleukin-6 receptor (IL-6R). All de novo transitional cell carcinomas, one squamous carcinoma, and two transitional cell carcinoma cell lines expressed the majority of HLA class II genes. All samples expressed IL-6R RNA whereas production of IL-6 message was limited to one of the cell lines and to the high-grade bladder cancers. These results were combined with stage, grade, and DNA content to develop a profile of the cancers examined. Although an improved predictive index based on gene expression analysis by RNA/PCR has not been realized, a broader survey of human tumors for expression of these genes and others is likely to refine the classification of bladder cancer.
Cancer 1991 Apr 15
PMID:Bladder cancer. Human leukocyte antigen II, interleukin-6, and interleukin-6 receptor expression determined by the polymerase chain reaction. 200 27


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