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)

Three highly homologous serine protease inhibitors, SPI-1, SPI-2 and SPI-3 (contrapsins), are synthesized in rat liver. Their expression is regulated differently in healthy and inflamed animals. We found that interleukin 6 (IL-6), a major acute phase cytokine, and to a lesser extent leukemia inhibitory factor (LIF), both together with glucocorticoids, are responsible for the regulation of expression of the contrapsins in rat hepatocytes in primary culture. The effect of IL-6 is time- and dose-dependent. IL-1, TGF beta 1, HGF, PMA and IL-8 did not have any effect on contrapsin mRNA levels. We postulate that SPI-1, SPI-2 and SPI-3 belong to the class II acute phase proteins. Additionally, we show induction of SPI-3 mRNA in rat liver by in situ hybridization using a specific oligonucleotide probe.
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PMID:Rat contrapsins are the type II acute phase proteins: regulation by interleukin 6 on the mRNA level. 751 32

Cytokine induction of intercellular adhesion molecule-1 (ICAM-1) in cardiac myocytes may be a critical step in inflammation associated with ischemia-reperfusion injury. We investigated the involvement of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and interleukin 8 (IL-8) on neutrophil-myocyte adhesion; These cytokines are increased in plasma of patients with acute myocardial infarction (AMI). ICAM-1 expression on cultured neonatal rat cardiac myocytes was determined through immunohistochemical and enzyme-linked immunosorbent assay (ELISA) analysis. ICAM-1 mRNA expression in myocytes was investigated by Northern blot hybridization. Rat neutrophils isolated from peripheral blood (PB) were used for adherence assay. In immunohistochemical study, cultured neonatal rat cardiac myocytes constitutively expressed ICAM-1 molecules. In ELISA analysis, ICAM-1 molecule expression on myocytes was significantly stimulated by TNF-alpha (100 U/ml), but not by IL-6 (100 U/ml) or IL-8 (100 ng/ml) dose dependently. The effect of TNF-alpha was observed as early as 6 h after stimulation. Levels of ICAM-1 mRNA were very low or almost undetectable in unstimulated myocytes, but its expression was markedly induced after exposure to TNF-alpha for 3 h. IL-6 and IL-8 showed no effect on ICAM-1 mRNA accumulation. Adhesion of rat neutrophils to myocytes was stimulated by TNF-alpha, and the effect of TNF-alpha on adherence was significantly inhibited by an anti-ICAM-1 monoclonal antibody (MoAb). These results show that TNF-alpha, but not IL-6 and IL-8, promotes neutrophil-myocyte adhesion through ICAM-1 expression, suggesting involvement of TNF-alpha in inflammation associated with ischemia-reperfusion injury.
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PMID:Neutrophil adherence to rat cardiac myocyte by proinflammatory cytokines. 751 17

We have examined basal and lipopolysaccharide (LPS)-induced release of interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), interleukin 8 (IL-8), tumour necrosis factor-alpha (TNF-alpha) and soluble CD14 (sCD14) in whole blood and peripheral blood mononuclear cells (PBMC) from 20 persons with either high (1.62-2.47 mmol/L) or low (0.43-1.29 mmol/L) levels of high-density lipoprotein (HDL). Whole blood was incubated at 37 degrees C for 2 h with 100 ng LPS/ml, while PBMC were incubated with 100 ng LPS/ml for up to 160 h. The LPS-induced release of IL-1 beta, IL-6, IL-8 and TNF-alpha into plasma showed no differences between the two HDL-groups; whereas levels of sCD14 were significantly higher in plasma in persons with low HDL (P < 0.01). PBMC incubated with LPS showed a significantly higher release of IL-1 beta (P = 0.01) and IL-6 (P = 0.02) in persons with high HDL at all sampling times. sCD14 was found not to be released by PBMC. These findings indicate that PBMC from persons with high or low levels of HDL have different functional properties, possibly of importance in inflammation and atherogenesis.
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PMID:LPS-induced release of IL-1 beta, IL-6, IL-8, TNF-alpha and sCD14 in whole blood and PBMC from persons with high or low levels of HDL-lipoprotein. 753 60

2B1 is a bispecific murine monoclonal antibody (BsMAb) with specificity for the c-erbB-2 and Fc gamma RIII extracellular domains. This BsMAb promotes the targeted lysis of malignant cells overexpressing the c-erbB-2 gene product of the HER2/neu proto-oncogene by human natural killer cells and mononuclear phagocytes expressing the Fc gamma RIII A isoform. In a Phase I clinical trial of 2B1, 15 patients with c-erbB-2-overexpressing tumors were treated with 1 h i.v. infusions of 2B1 on days 1, 4, 5, 6, 7, and 8 of a single course of treatment. Three patients were treated with daily doses of 1.0 mg/m2, while six patients each were treated with 2.5 mg/m2 and 5.0 mg/m2, respectively. The principal non-dose-limiting transient toxicities were fevers, rigors, nausea, vomiting, and leukopenia. Thrombocytopenia was dose limiting at the 5.0 mg/m2 dose level in two patients who had received extensive prior myelosuppressive chemotherapy. Murine antibody was detectable in serum following 2B1 administration, and its bispecific binding properties were retained. The pharmacokinetics of this murine antibody were variable and best described by nonlinear kinetics with an average t 1/2 of 20 h. Murine antibody bound extensively to all neutrophils and to a proportion of monocytes and lymphocytes. The initial 2B1 treatment induced more than 100-fold increases in circulating levels of tumor necrosis factor-alpha, interleukin 6, and interleukin 8 and lesser rises in granulocyte-monocyte colony-stimulating factor and IFN-gamma. Brisk human anti-mouse antibody responses were induced in 14 of 15 patients. Several minor clinical responses were observed, with reductions in the thickness of chest wall disease in one patient with disseminated breast cancer. Resolution of pleural effusions and ascites, respectively, were noted in two patients with metastatic colon cancer, and one of two liver metastases resolved in a patient with metastatic colon cancer. Treatment with 2B1 BsMAb has potent immunological consequences. The maximum tolerated dose and Phase II daily dose for patients with extensive prior myelosuppressive chemotherapy was 2.5 mg/m2. Continued dose escalation is required to identify the maximally tolerated dose for patients who have been less heavily pretreated.
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PMID:Phase I trial of 2B1, a bispecific monoclonal antibody targeting c-erbB-2 and Fc gamma RIII. 755 34

It has been reported that interleukin 8 (IL-8) and interleukin 6 (IL-6) are two of the chemical mediators causing myocardial injury. It is not clear whether treatment with corticosteroids in vitro in these patients can prevent the production of interleukin 8 and 6. This prospective study was conducted to investigate whether methylprednisolone (MP) pretreatment (30 mg.kg-1 before CPB and before declamping of aorta) influenced the production of IL-8 and 6 in the peripheral circulation in 27 patients undergoing elective coronary artery bypass surgery. The IL-8 and IL-6 concentrations were measured by ELISA kit. We also studied the effect of MP pretreatment on postoperative cardiac function. Serum concentration of IL-8 in non-MP-treated patients (37 +/- 44 pg.ml-1 preoperatively) increased to 169 +/- 86 pg.ml-1 60 min after declamping of the aorta (P < 0.001). The increase was greater than the increase from 22 +/- 8.9 pg.ml-1 to 52 +/- 35 pg.ml-1 in the MP-treated patients (P < 0.01). Serum IL-6 concentration in non-MP-treated patients increased from the preoperative value of 59 +/- 30 pg.ml-1 to 436 +/- 143 pg.ml-1 60 min after declamping of the aorta (P < 0.001). The increase was greater than the increase from 36 +/- 15 pg.ml-1 to 135 +/- 85 pg.ml-1 in the MP-treated patients (P < 0.01). Furthermore, postoperative cardiac index in MP-treated patients (3.6 +/- 1.1 L.min-1.m-2) was higher than 2.3 +/- 0.8 L.min-1.m-2 of non MP-treated patients (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Methylprednisolone inhibits increase of interleukin 8 and 6 during open heart surgery. 761 47

We determined the levels of inflammatory cytokines such as interleukin 6 (IL-6) granulocyte-colony stimulating factor (G-CSF) and IL-8 in the amniotic fluids from women with premature or term delivery. Cytokines were detectable even in the absence of apparent infection (group 1), but much higher cytokine levels were found in cases of intrauterine infection, particularly in cases of premature delivery (group 2). In cases of term delivery (groups 3-5), all of the cytokine levels showed c. 3- to 4-fold increase during labor pain (group 4) and an 8- to 13-fold increase in the presence of endotoxin (group 5), in comparison with the levels in cases where neither factor was present (group 3). Regarding infection, the cytokine levels were 20- to 30-fold higher in chorioamnionitis-positive premature delivery group (group 2), than in the infection-negative group (group 1). All the cytokines were simultaneously induced in amniotic fluid by labor pain and infection, and a significant positive correlation was observed among these three cytokine levels. In-vitro culture system and immunohistochemical study indicated that the cytokines in the amniotic fluid appeared to originate from trophoblasts and decidual cells. Thus, infection and labor pain may trigger the production of inflammatory cytokines at term as well as premature delivery and the determination of these cytokine levels will be a good indication for the prediction of the presence of intrauterine infection.
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PMID:Elevation of amniotic fluid interleukin 6 (IL-6), IL-8 and granulocyte colony stimulating factor (G-CSF) in term and preterm parturition. 768 6

Pulmonary fibrosis corresponds to an accumulation of collagens and other proteins of the extracellular matrix in the interstitium and alveoli. Biochemical and cellular mechanisms of pulmonary fibrogenesis remain poorly understood. The cells of the alveolitis (macrophages, lymphocytes and neutrophils) play a key role in producing the factors which regulate the proliferation, chemotactism and secretory activity of the fibroblasts. Amongst these factors the cytokines (interleukins, interferons and growth factors) play a definite but very complex role. Certain cytokines stimulate in vitro the attraction and activation of cells of the alveolitis, as well as the multiplication, migration and secretory activity of fibroblasts. The following cytokines are involved: tumour necrosis factor alpha: (TNF alpha), interleukin 1 (IL-1), interleukin 6 (IL-6) interleukin 8 (IL-8) transforming growth factor beta (TGF beta), platelet derived growth factor (PDGF), insulin like growth factor 1 (IGF-1), fibronectin, monocyte chemotactic protein 1: (MCP-1). Other cytokines, principally the interferons (of alpha, beta or gamma type: IFN alpha, IFN beta, IFN gamma) inhibit in vitro and in vivo the proliferation and the production of collagen by fibroblasts. During the course of human pulmonary fibrosis or in experimental situations, the majority of the cytokines mentioned above are produced in excess in the lung. Without doubt they play an important role in the pathogenesis of fibrosis, even if it is not yet very well known how they interact and contribute in vitro to the process of fibrogenesis. Certain cytokines potentially regulating in the fibrosis are yet to be identified. In the future the use of cytokines and of their inhibitors will perhaps provide new therapies in pulmonary fibrosis.
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PMID:[Cytokines and pulmonary fibroses]. 768 79

Cardiac surgery, employing cardiopulmonary by-pass (CPB), has long been associated with a generalized immunosuppression. To further understand the complex physiological and immunological changes related to CPB, we decided to investigate whether CPB affects the immune response, with regard to T-cell activation and cytokine production. Using phytohaemagglutinin (PHA) as mitogen and peripheral blood mononuclear cells (PBMC) isolated from patients undergoing CPB, we investigated whether this procedure has any effect on interferon-gamma(IFN-gamma) and other cytokine production and/or PBMC proliferation. Comparisons were made between the responsiveness of PBMC obtained before, during and at the end of CPB. In all patients, CPB significantly reduces IFN-gamma and interleukin 2 (IL-2) production in response to PHA. On the other hand, tumour necrosis factor-alpha (TNF-alpha) production was also significantly diminished, while interleukin 6 (IL-6), interleukin 1 beta (IL-1 beta) and interleukin 8 (IL-8) release in response to PHA was not significantly affected. Reduced IFN-gamma, IL-2 and TNF-alpha production was associated with a significant decrease in PBMC proliferation. These results might be related to the mechanical damage on blood cells described during extracorporeal circulation procedures as well as the release of immunosuppressive factors during surgery. The immunosuppression observed during CPB may play an important role in the development of infectious complications after CPB.
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PMID:In vitro cytokine production and T-cell proliferation in patients undergoing cardiopulmonary by-pass. 778 36

Patients with head injury must overcome central as well as peripheral metabolic insults. In addition to specific tissue damage to the brain, a cellular biochemical cascade occurs that can negatively affect organ function, cause a systemic response to injury, and may cause secondary tissue injury. The metabolites involved in this cascade are numerous and complex. Cytokines are important cell-to-cell communication mediators during injury. It is speculated that cytokines, such as interleukin 1 (IL-1), interleukin 6 (IL-6), tumor necrosis factor (TNF), and interleukin 8 (IL-8), which are found in elevated amounts in both human and basic trials after head injury, play a role in the cellular cascade of injury. Some of the metabolic events produced by small doses of cytokine infusion in animals, as well as humans, include fever, neutrophilia, muscle breakdown, altered amino acid metabolism, depression of serum zinc levels, production of hepatic acute phase reactants, increased endothelial permeability, and expression of endothelial adhesion molecules. These are all known sequelae of severe head injury. Cytokines have also been implicated in organ failure. Infusion of cytokines in basic science trials revealed that organ functions of the gut, liver, and lung are negatively altered by high-dose cytokine infusion. Infusion of certain cytokines has been shown to cause death of brain cells, increase blood-brain barrier permeability, and cause cerebral edema. This suggests that cytokines may also play a role in the sequelae of organ demise. These effects of cytokines have been attenuated in basic trials by blocking the initial signaling system of cytokines or by decreasing serum cytokine activity. We hypothesize that cytokines that are elevated after head injury play a role in the pathology of injury, including altered metabolism and organ demise.
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PMID:Cytokines and metabolic dysfunction after severe head injury. 786 40

Women with breast cysts lined by apocrine epithelium (intracystic Na/K < 3) may have a higher risk of developing breast cancer than those whose breast cysts are lined by "flattened" epithelium (intracystic Na/K < 3). In this study, the concentrations of the cytokines, oncostatin M (OSM), interleukin 2 (IL-2), interleukin 6 (IL-6) and interleukin 8 (IL-8) were measured in breast cyst fluid, OSM, IL-2 and IL-6 having been shown to have growth-inhibitory actions on tumour cells. All cytokines were measured by "sandwich" enzyme immunoassays. IL-2 was not detectable in breast cyst fluid. OSM, IL-6 and IL-8 concentrations were significantly higher in the high-electrolyte-ratio group. Although significant positive correlations were found between OSM and IL-6, OSM and IL-8, OSM and Na/K, IL-6 and IL-8, IL-6 and Na/K and IL-8 and Na/K when all samples were analysed together, analysis of the correlations between these analytes in each subgroup separately suggests that the control of production of these cytokines or the mechanism of entry into cyst fluid is likely to be different for the 2 cyst types. The significantly higher intracystic concentrations of OSM and IL-6 in the high-electrolyte-ratio group may partly explain the lower risk of breast cancer in this group of women.
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PMID:Oncostatin M, interleukin 2, interleukin 6 and interleukin 8 in breast cyst fluid. 792 43


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