Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of the present study was to investigate the effects of isolated limb perfusion (ILP) with tumour necrosis factor alpha (TNF-alpha) and melphalan in patients with cancer on, first, plasma levels of cytokines, second, systemic monocyte and T-lymphocyte distribution and, third, the ability of mononuclear cells to produce cytokines upon stimulation in vitro. Six patients undergoing an ILP were entered into the study (group 1). In addition, patients undergoing a major surgical operation (group 2) minor operation (group 3) as well as healthy volunteers (group 4) were included as control groups. Sensitive enzyme-linked immunosorbent assays (ELISAs) were used to measure TNF-alpha and interleukin-6 (IL-6) plasma levels at various time points during and after operation. Furthermore, the percentage of monocytes and T lymphocytes was determined in all studied groups using a FACScan. In addition, cytokine production upon stimulation with lipopolysaccharide (LPS) and a combination of anti-CD3/anti-CD28 monoclonal antibodies in whole-blood cultures was investigated. Increased plasma levels of TNF-alpha and IL-6 in patients undergoing ILP was observed, but only IL-6 appeared to be increased in patients treated with a major operation. No significant fluctuations were found in the other groups studied. Concerning the number of monocytes, a significant decrease was observed only in patients treated with ILP. Furthermore, a decreased production of TNF-alpha, IL-6 and IL-8 upon various types of stimulation in vitro was found in those patients, but also after a major operation. In conclusion, the results of the present study show increased plasma levels of cytokines in patients treated with ILP and major operation. Furthermore, a decrease in numbers of monocytes in the circulation and the ability of mononuclear cells to produce cytokines in vitro may be induced by administration of TNF-alpha in ILP. Although similar results were found in patients treated with major operation, the underlying mechanisms of this phenomenon remain to be elucidated.
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PMID:Effects of isolated limb perfusion with tumour necrosis factor-alpha on the function of monocytes and T lymphocytes in patients with cancer. 901 83

Interleukin-8 (IL-8) is a member of the chemokine family of pro-inflammatory chemotactic cytokines and is secreted by some human colorectal carcinoma cell lines. We have used in situ hybridisation and immunohistochemistry to determine whether IL-8 mRNA and protein, respectively, are produced by human colorectal carcinoma cells in vivo. IL-8 mRNA was detected within the cytoplasm of tumour cells in all nine samples tested, including that of a tumour which had metastasised to a lymph node. Non-involved colonic mucosa within the same tissue blocks showed much weaker labelling. IL-8 protein was detected in 74% (23/31) of tumour samples and was mainly localised to the tumour cell cytoplasm. In 30% of cases, staining was heterogeneous, with between 1 and 30% of cells being positive. In some tumour cells, IL-8 showed a perinuclear distribution resembling that found by in situ hybridisation. Some infiltrating leucocytes, endothelial cells and fibroblast-like cells within the tumour sections were also positive for IL-8 mRNA and protein. The possibilities that colorectal tumours produce IL-8 to aid invasion and/or metastasis or as a tumour growth factor are discussed.
Eur J Cancer 1996 Nov
PMID:Detection of interleukin-8 mRNA and protein in human colorectal carcinoma cells. 901 58

The hypothyroid state or nonthyroidal illness is often observed in patients with recurrent cancer. High levels of cytokines are frequently observed in critically ill patients. Recent studies have shown that interleukin (IL)-6 may be a cause of nonthyroidal illness. We reported the relationship between thyroid function and the prognosis of the patients with recurrent breast cancer. In this study, we measured the serum level of cytokines (IL-2, IL-6, IL-8) and thyroid function (free T3, free T4, and thyrotropin (TSH)) in 38 patients with recurrent breast cancer. All patients had received three or more different courses of therapy before they were entered the study. The patients were divided into three groups according to their response to therapy. There were 16 partial response (PR), 10 no change (NC) and 11 progressive disease (PD) patients. They did not receive any medication that influenced the thyroid hormone level other than medication for cancer. The IL-2 level was under the detectable limit in all groups. No abnormal levels of cytokines were observed in the PR group. IL-6 and IL-8 levels in the PD group were significantly higher than that in the NC group (p < 0.05). Significant negative correlation was observed between IL-6 and thyroid hormones (free T3, free T4). Patients whose IL-6 level was 20 pg/ml or more died within four months after the beginning of the treatment. We concluded that IL-6 may lead to a hypothyroid state in patients with recurrent breast cancer. A high level of IL-6 and IL-8 means the confusion of the defense system in hosts. Therefore, these cytokines will be predictive indicators of the therapeutic response and the prognosis of the patients with recurrent breast cancer.
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PMID:Changes of cytokines and thyroid function in patients with recurrent breast cancer. 906 4

We reported earlier that IL-1 inhibits the growth of human melanoma cells (A375-6), and that these cells become resistant to IL-1 after prolonged periods of culture. The resistant cells constitutively produce IL-alpha and IL-6 with IL-6 production was induced by endogenous IL-1 in an autocrine manner. The cells are also resistant to IL-6 anti-proliferative effects. In the present study, we show that the resistant clones exhibited up-regulated expression of intercellular-adhesion molecule 1 (ICAM-1) and vitronectin receptor (integrin alpha(v)beta3) when compared with the IL-1-sensitive clone, A375-6. Moreover, these IL-1-resistant clones exhibited many other metastatic characteristics, such as expression of IL-8 mRNA, production of matrix metalloproteinases (MMP-2 and MMP-9), and augmented invasion activity. However, contrary to our expectations, the IL-1-resistant cells did not exhibit experimental metastasis in a nude-mouse model, similarly to the IL-1-sensitive parental A375-6 cell line. In contrast, the highly metastatic clone A375-SM exhibited alpha(v)beta3 expression at a level comparable to that of the IL-1-resistant cells, but expressed low or no ICAM-1, metalloproteinase and displayed little in vitro invasion activity. These results show that the metastatic characteristics of IL-1-resistant cells are not sufficient to produce metastasis in vivo and suggest that these resistant clones may provide a good model system for characterizing the molecular mechanisms of metastasis.
Int J Cancer 1997 May 02
PMID:Resistance to IL-1 anti-proliferative effect, accompanied by characteristics of advanced melanoma, permits invasion of human melanoma cells in vitro, but not metastasis in the nude mouse. 913 78

Serum levels of group II phospholipase A2 (PLA2) have been reported to be associated with stage of disease in cancer patients. These levels are also related to the malignant potential in tissues, and are an important prognostic factor. We radioimmunoassayed group II PLA2 levels in pleural and peritoneal effusions from patients with various cancers. We also investigated the production of group II PLA2 in cells in effusions from cancer patients by Northern blotting, immunocytochemistry and in situ hybridization. Immunoreactive group II PLA2 levels were significantly higher in effusions from 47 patients with various cancers, compared with those in sera and cirrhotic ascites. There was no significant correlation between group II PLA2 levels in effusions and those in sera. Group II PLA2 mRNA was expressed at a high level in cells from effusions, by Northern blot analysis, but not in those cells from blood. The localization of group II PLA2 protein and mRNA was intense in carcinoma cells and CD68-positive macrophages, determined by immunocytochemistry and in situ hybridization. In addition, IL-6 and IL-8 levels were significantly higher in effusions, in comparison with those in sera from patients, suggesting that cancer cells and macrophages produce group II PLA2 by IL-6. These group II PLA2 levels are apparently significantly increased in effusions, and the carcinoma cells and macrophages produce group II PLA2, as noted in effusions from patients with various cancers.
Int J Cancer 1997 Jun 20
PMID:Group II phospholipase A2 is increased in peritoneal and pleural effusions in patients with various types of cancer. 922 99

Bladder cancer cells have been shown to secrete a variety of factors that are not related to cells of urothelial origin. The histogenesis of these tumour developments is uncertain, and a variety of theories have been previously reported. In the present manuscript, we identify the factors constitutively produced by a human bladder cancer cell line (KU-19-19) that was found to produce beta human chorionic gonadotrophin (beta-hCG), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 1alpha (IL-1alpha), interleukin 6 (IL-6) and interleukin 8 (IL-8). The cells were obtained from a case of metastatic carcinoma that was originally diagnosed to be a grade 3 (WHO classification), invasive transitional cell carcinoma of the bladder. On microscopic observation, the cultured cells exhibited an epithelial appearance with vacuole formation in their cytoplasm. Ultrastructural observations revealed relatively marked microvilli and a tight junction. Significant amounts of beta-hCG, G-CSF, GM-CSF, IL-1alpha, IL-6 and IL-8 concentrations in the supernatant from cultured cells were demonstrated by enzyme-linked immunosorbent assays, while the expression of mRNA of these marker proteins in cancer cells was also significantly exhibited by reverse transcription polymerase chain reaction (RT-PCR). In addition, the expression of G-CSF receptor and IL-6 receptor mRNA was also shown by RT-PCR. Xenograft transplantability using nude mice was observed in association with the presence of severe neutrophilia in the peripheral blood. These results indicate that this cell line appears to be an effective model for the study of transitional cell carcinoma of the bladder with multipotent differentiation potentials.
Br J Cancer 1997
PMID:Constitutive production of multiple cytokines and a human chorionic gonadotrophin beta-subunit by a human bladder cancer cell line (KU-19-19): possible demonstration of totipotential differentiation. 923 15

Interfering with the endotoxin-mediated cytokine cascade is thought to be a promising approach to prevent septic complications in gram-negative infections. The synthetic lipid A analog SDZ MRL 953 has been shown to be protective against endotoxic shock and bacterial infection in preclinical in vivo models. As part of a trial of unspecific immunostimulation in cancer patients, we conducted a double-blind, randomized, vehicle-controlled phase I trial of SDZ MRL 953 to investigate, first, its biologic effects and safety of administration in humans and, second, its influence on reactions to a subsequent challenge of endotoxin (Salmonella abortus equi). Twenty patients were treated intravenously with escalating doses of SDZ MRL 953 or vehicle control, followed by an intravenous application of endotoxin (2 ng/kg of body weight [BW]). Administration of SDZ MRL 953 was safe and well-tolerated. SDZ MRL 953 itself increased granulocyte counts and serum levels of granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6), but not of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), IL-1beta, and IL-8. Compared with vehicle control, pretreatment with SDZ MRL 953 markedly reduced the release of TNF-alpha, IL-1beta, IL-8, IL-6, and G-CSF, but augmented the increase in granulocyte counts to endotoxin. Induction of tolerance to the endotoxin-mediated cascade of proinflammatory cytokines by pretreatment with SDZ MRL 953 in patients at risk may help to prevent complications of gram-negative sepsis.
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PMID:Downregulation of the proinflammatory cytokine response to endotoxin by pretreatment with the nontoxic lipid A analog SDZ MRL 953 in cancer patients. 926 88

Intestinal epithelial cells produce various inflammatory mediators. However, the way in which immunosuppressive agents influence the production of these mediators by intestinal epithelial cells is not understood. The effects of cyclosporine A (CsA), tacrolimus (FK506), and dexamethasone (DEX) on cytokine-induced production of interleukin (IL)-8 in a human colonic cancer cell line (HT-29) were examined. HT-29 cells were stimulated with either IL-1 beta or tumor necrosis factor alpha (TNF alpha) together with CsA, FK506, or DEX. The presence of IL-8 protein was detected by enzyme-linked immunosorbent assay, and the expression of IL-8 messenger RNA (mRNA) by reversetranscription polymerase chain reaction. CsA (1, 5, and 10ng/ml) significantly reduced IL-1 beta-induced IL-8 production (by 32%, 41%, and 48%, respectively), and reduced TNF alpha-induced IL-8 production (by 21%, 42%, and 50%, respectively). FK506 or DEX had no effect on IL-1 beta- or TNF alpha-induced IL-8 production. The expression of IL-8 mRNA was also inhibited by CsA. These findings suggest that CsA may influence the production of inflammatory mediators in colonic cells in a different manner from FK506 and DEX.
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PMID:Cyclosporine A inhibits interleukin-8 production in a human colon epithelial cell line (HT-29). 934 85

High-dose interleukin-2 (IL-2) treatment has demonstrated promising antitumour activity in renal cell carcinoma (RCC) and malignant melanoma (MM) and has been shown to induce broad immunological effects. The optimal IL-2 dose and schedule, however, still remain to be defined. We studied a treatment protocol consisting of five repetitive cycles of high-dose recombinant (rh) IL-2 (24 x 10(6) U/m2/day) administered weekly on two consecutive days by continuous intravenous infusion. 17/19 were RCC patients, 2 of whom responded with a complete remission (CR) and 3 with a partial response (PR) (CR + PR: 29%; median response duration of 11.5+ months (range: 3-14 months)). IL-2 induced a pronounced increase of lymphocytes and pro-inflammatory cytokines IL-8, IL-5, gamma-IFN, TNF- alpha and TNF-beta (p < 0.05) that peaked in cycle 3. With subsequent therapy, serum levels of these cytokines, NK, T cells and eosinophils decreased, whereas serum IL-10 levels progressively increased with maximum levels achieved after the fifth week of treatment, suggesting that it may be involved in dampening the inflammatory response induced by IL-2. Absolute numbers of activated T cells and NK cells remained elevated as compared to baseline for at least 4 weeks after treatment cessation. Based on these observations, future scheduling of IL-2 will be done at 3 weekly 2-day cycles separated by a week 4 treatment-free interval in order to increase further the 29% objective response rate achieved in this study.
Eur J Cancer 1997 Jun
PMID:Clinical and immunomodulatory effects of repetitive 2-day cycles of high-dose continuous infusion IL-2. 937 86

The presence of mRNA transcripts for cytokines in normal and neoplastic human breast tissue has been investigated. Using reverse transcriptase-linked polymerase chain reaction (RT-PCR), we have specifically screened for the following cytokines: interleukin (IL)-1alpha, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, tumour necrosis factor (TNF)-alpha, TNF-beta and interferon (IFN)-gamma. No significant differences in expression of IL-1alpha, IL-1beta, IL-4, IL-6, TNF-alpha or TNF-beta were observed between the 2 groups of tissues. However, there was a significant difference in expression of IL-8 transcripts (p = 0.0017) which was higher in the neoplastic population. Transcripts for IL-2, IL-3, IL-5, IL-7 and IFN-gamma were not detected in either group. There was no evidence of associations between cytokine expression and tumour histological grade, patient age or lymph node metastases. Correlating tumour types with specific cytokine transcripts revealed high expression of IL-8, and to a lesser extent, IL-8 and TNF-beta irrespective of tumour origin. Analysis of primary epithelial and stromal cultures derived from both types of tissue showed that increased levels of IL-8, but not IL-6, were secreted by cells obtained from tumours. Thus, breast tissue of both normal and neoplastic origin expresses a wide range of cytokines. Increased or aberrant expression of cytokines, in particular IL-8, may be involved in the development/progression of breast cancer.
Int J Cancer 1997 Sep 17
PMID:Expression of cytokine messenger RNA in normal and neoplastic human breast tissue: identification of interleukin-8 as a potential regulatory factor in breast tumours. 937 54


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