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

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

The eradication of minimal residual blast populations by activation of autologous cytotoxic cells with interleukin 2 (IL-2) is a new promising tool in the treatment of acute myelocytic leukemia (AML). However, the immunological effector cells are not yet clearly defined. The present study was designed to investigate the presence of cytotoxic precursor cells in active AML and to identify phenotypical and functional characteristics of autologous anti-leukemic cytotoxic effector cells. For this purpose, mononuclear cells (MNC) containing at least 70% leukemic blasts were isolated from bone marrow of untreated AML and cultured in the presence of 3000 IU/ml recombinant IL-2 (rIL-2) for 6-8 weeks. Under these conditions, T-cells were selected in the bone marrow cultures and overgrew the leukemic blasts. The resulting T-cell populations were cloned by limiting dilution and the clones obtained were characterized for their phenotypical and functional patterns. Totally, cloning resulted in 68 clones and a few cell lines. The clonality was verified by RT PCR analysis of TCR V beta gene expression. All clones obtained stained positive for CD2, CD3, DR and CD56. The vast majority (68%) of T-cell clones/lines was CD4+, a few clones expressed CD8 (19%) or CD4 and CD8, and four clones were of TCR gamma delta origin. Seven of 15 clones tested, including three CD4+, two CD8+ and two TCR gamma delta(+)-clones were found to be cytotoxic against autologous leukemic blast cells. All except one clone expressed oncolytic activities against allogeneic blasts too. One of the TCR gamma delta(+)-clones demonstrated NK activity by lysis of K562 targets. The majority of the T-cell-clones released IL-2, IL-8, TNF-alpha, GM-CSF but only a few IFN gamma and expressed high levels of mRNA for IL-2, TGF-beta and IL-10. None of the clones was found to produce IL-3, IL-4, IL-7 and TNF-beta. The data provide evidence of the existence of T-cell precursors in untreated AML bone marrow differentiating to cytotoxic cells with activity against autologous and allogeneic AML blast cells.
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PMID:Bone marrow-derived T-cell clones obtained from untreated acute myelocytic leukemia exhibit blast directed autologous cytotoxicity. 786 44

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

Knowledge of the aetiology and pathogenesis of the inflammation in ulcerative colitis and Crohn's disease is still insufficient. It is thought that some antigen is the trigger which induces a chain of immune reactions but the origin of this antigen has not so far been elucidated. In theory, an antigen-presenting cell forms a complex with endotoxin-derived peptides as antigen. T-helper lymphocytes recognize this complex, are activated and start to produce cytokines. For inflammatory bowel diseases (IBD) the most important cytokines identified are interleukin 1 (IL-1), interleukin 2 (IL-2), interleukin 6 (IL-6), interleukin 8 (IL-8), gamma-interferon (G-IFN), and tumor necrosis factor-alpha (TNF-alpha). Inhibition of these cytokines can be achieved by administration of cyclosporine, which inhibits the function of T-helper lymphocytes. Orally, intravenously, and locally administered cyclosporine is able to improve the disease activity in ulcerative colitis and Crohn's disease, but its use is limited because of side-effects. The novel immunosuppressant FK506 has comparable actions to cyclosporine in regulating cytokine production and may even be more effective than cyclosporine. The receptor antagonist of IL-1 (IL-1ra) competitively binds to the IL-1 receptor located on several lymphocytes. Treatment of animals with IL-1ra has been successful and clinical trials using recombinant IL-1ra are underway in IBD. Antibodies against alphaIL-2r have also been used successfully in animal studies. No experience with this substance has been obtained in man. The use of alpha-interferon seems to be effective in some patients with Crohn's disease. CD4 and CD8 molecules on lymphocytes are needed to form the interaction between antigen, antigen-presenting cell, and lymphocytes. Specific monoclonal antibodies against CD4 are successfully used in patients with active ulcerative colitis and Crohn's disease. TNF-alpha shares many of the proinflammatory activities of IL-1. In preliminary studies, especially in patients with Crohn's disease, the effects of the administration of antibodies to TNA-alpha were excellent.
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PMID:Selective immunomodulation in patients with inflammatory bowel disease--future therapy or reality? 881 2

Our purpose was to determine the effective biological dose and/or maximum tolerated dose of recombinant human tumor necrosis factor receptor:IgG chimera (rhuTNFR:Fc; Immunex, Seattle, WA) in combination with interleukin 2 (IL-2) with regard to reduction in IL-2 toxicity and modulation of biological effects of high-dose IL-2 administration. Twenty-four patients with metastatic cancer were treated with escalating doses of rhuTNFR:Fc at 1, 1, 5, 10, and 20 mg/m2 i.v. on days 1 and 15 (dose levels 1-5) or 10, 20, and 30 mg/m2 days 1 and 15 plus 50% dose on days 3, 5, 17, and 19 (dose levels 6-8) prior to IL-2 at doses of 300,000 IU/kg (dose level 1) and 600,000 IU/kg (dose levels 2-8) i.v. every 8 h on days 1-5 and 15-19. The t1/2 of rhuTNFR in patients receiving IL-2 was 72 h. The median number of IL-2 doses was 24, and central nervous system, skin, and cardiac arrhythmias were the major dose-limiting toxicities. TNF bioactivity was inhibited, and the polymorphonuclear leukocyte chemotactic defect normally seen with IL-2 was not observed. Increases in C-reactive protein, IL-6, IL-8, and IL-1 receptor antagonist levels were partially suppressed relative to historical controls, whereas peripheral blood mononuclear cell phenotypes, urinary nitrate, endothelial adhesion molecule expression in skin biopsies, and cellular infiltrates in tumor biopsies were consistent with findings in patients treated with IL-2 alone. Four patients developed thyroid dysfunction. There were five responses: two complete responses (both melanoma) and three partial responses (response rate, 21%). rhuTNFR:Fc may modulate the toxicity and some of the biological effects of IL-2 while preserving antitumor activity. Dose level 6 (10 mg/m2 on days 1 and 15, and 5 mg/m2 on days 3, 5, 17, and 19) has been chosen for a randomized, double-blind, placebo-controlled trial of IL-2 with and without rhuTNFR:Fc.
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PMID:Phase I trial of interleukin 2 in combination with the soluble tumor necrosis factor receptor p75 IgG chimera. 981 6

Allogeneic bone marrow transplantation was performed in a 24-year-old woman with acute myelogenous leukemia in the first remission (FAB classification: M4). Graft-versus-host disease occurred from around day 150 after bone marrow transplantation. The levels of tumour necrosis factor-alpha, interleukin 12, and intercellular adhesion molecule-1 were elevated in the early stage of graft-versus-host disease, followed by elevation of interleukin 10 and interleukin 8. Her symptoms subsequently improved and all of these parameters became normal. The levels of thrombomodulin and plasminogen activator inhibitor type 1 showed changes that were in parallel with the clinical course. Interleukin 1beta, interleukin 6, interleukin 2, and interferon-gamma showed no changes throughout the course of her graft-versus-host disease. These findings suggested the possibility that release of inflammatory molecules occurred at the onset of graft-versus-host disease and caused vascular endothelial damage, which led to the exacerbation of her disease.
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PMID:Changes of cytokines during the course of graft-versus-host disease following bone marrow transplantation: a case report. 1093 Mar

A gradual decline in the functional activity of the immune system is described with advancing age. The adaptive immune system seems the most severely affected, but some age-associated modifications also occurs in NK cells. Several studies investigated the age related changes of cytokine production, while little is known about chemokines, whose importance in regulating immune-response becomes even more evident. In this study we investigated whether the ability of T lymphocytes and NK cells to produce IL-8, either spontaneously or after activation, respectively with anti-CD3 monoclonal antibody or interleukin 2 (IL-2) was affected by age. We demonstrated that: (a) T lymphocytes and NK cells spontaneously produced detectable amounts of IL-8; (b) anti-CD3 stimulation of T lymphocytes significantly increased IL-8 production and the increment was more evident in the nonagenarian subjects; (c) similarly, IL-2 stimulation of NK cells rose the production of IL-8 but the amount produced by the old was lower than the one produced by the young group. Because of the co-stimulatory role of chemokines on NK responses and given the demonstrated importance of NK cells in defence against viral infections, the decreased production of IL-8 can be involved in the defective functional activity of NK cells from old subjects.
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PMID:Different IL-8 production by T and NK lymphocytes in elderly subjects. 1147 Jan 28

Cytokines function at the cellular, microenvironmental level, but human cytokine assessment is most commonly done at the macro level, by measuring serum cytokines. The relationships between serum and cellular cytokines, if there are any, are undefined. In a study of hospitalized patients in Malawi, we compared cytometrically assessed, cell-specific cytokine data to serum interleukin 2 (IL-2), IL-4, IL-6, IL-8, IL-10, gamma interferon (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) levels in 16 children and 71 (IL-2, -4, -6, -10) or 159 (IL-8, IFN-gamma, and TNF-alpha) adults, using Wilcoxon rank sum tests and Pearson's (r(p)) and Spearman's (r(s)) rank correlations. For the entire study group, correlations between identical serum and cellular cytokines mainly involved IL-8 and IFN-gamma, were few, and were weakly positive (r < 0.40). Blood culture-positive persons had the most and strongest correlations, including those between serum IL-2 levels and the percentages of lymphocytes spontaneously making IL-2 (r(s) = +0.74), serum IL-8 levels and the percentages of lymphocytes spontaneously making IL-8 (r(p) = +0.66), and serum IL-10 levels and the percentages of CD8(+) T cells making TNF-alpha (r(p) = +0.89). Human immunodeficiency virus (HIV)-positive persons had the next largest number of correlations, including several serum IL-8 level correlations, correlation of serum IL-10 levels with the percentages of lymphocytes producing induced IL-10 (r(s) = +0.36), and correlation of serum IFN-gamma levels and the percentages of lymphocytes spontaneously making both IL-6 and IFN-gamma in the same cell (r(p) = +0.59). HIV-negative, malaria smear-positive, and pediatric patients had few significant correlations; for the second and third of these subgroups, serum IL-8 level was correlated with the percentage of CD8(-) T cells producing induced IL-8 (r(s) = +0.40 and r(s) = +0.56, respectively). Thus, the strength of associations between serum and cellular cytokines varied with the presence or absence of bloodstream infection, HIV status, and perhaps other factors we did not assess. These results strongly suggest that serum cytokines at best only weakly reflect peripheral blood cell cytokine production and balances.
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PMID:Comparison of serum and cell-specific cytokines in humans. 1168 46

We investigated levels of maternal cytokines in late pregnancy in relation to the subsequent development of adult schizophrenia and other psychoses in their offspring. The sample included the mothers of 27 adults with schizophrenia and other psychotic illnesses and 50 matched unaffected controls from the Providence cohort of the Collaborative Perinatal Project. Serum samples were analyzed for interleukin 1 beta (IL-1-beta), interleukin 2 (IL-2), interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis factor alpha (TNF-alpha) by enzyme immunoassay. Maternal levels of TNF-alpha were significantly elevated among the case series (t = 2.22, p =.04), with evidence of increasing odds of psychosis in relation to higher cytokine levels. We did not find significant differences between case and control mothers in the serum levels of IL-1, IL-2, IL-6, or IL-8. These data support previous clinical investigations reporting maternal infections during pregnancy as a potential risk factor for psychotic illness among offspring.
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PMID:Maternal cytokine levels during pregnancy and adult psychosis. 1178 7

Cytokines regulate cellular immune activity and are produced by a variety of cells, especially lymphocytes, monocytes, and macrophages. Multiparameter flow cytometry is often used to examine cell-specific cytokine production after in vitro phorbol 12-myristate 13-acetate and ionomycin induction, with brefeldin A or other agents added to inhibit protein secretion. Spontaneous ex vivo production reportedly rarely occurs. We examined the spontaneous production of interleukin 2 (IL-2), IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-alpha), and gamma interferon (IFN-gamma) by peripheral-blood B lymphocytes, T cells, CD8(-) T cells, CD8(+) T cells, CD3(-) CD16/56(+) lymphocytes (natural killer [NK] cells), CD3(+) CD16/56(+) lymphocytes (natural T [NT] cells), and/or monocytes of 316 acutely ill hospitalized persons and 62 healthy adults in Malawi, Africa. We also evaluated the relationship between spontaneous and induced cytokine production. In patients, spontaneous TNF-alpha production occurred most frequently, followed in descending order by IFN-gamma, IL-8, IL-4, IL-10, IL-6, and IL-2. Various cells of 60 patients spontaneously produced TNF-alpha; for 12 of these patients, TNF-alpha was the only cytokine produced spontaneously. Spontaneous cytokine production was most frequent in the immunoregulatory cells, NK and NT. For IL-2, IL-4, IL-6, IL-8, and IL-10, spontaneous cytokine production was associated with greater induced production. For TNF-alpha and IFN-gamma, the relationships varied by cell type. For healthy adults, IL-6 was the cytokine most often produced spontaneously. Spontaneous cytokine production was not unusual in these acutely ill and healthy persons living in an area where human immunodeficiency virus, mycobacterial, malaria, and assorted parasitic infections are endemic. In such populations, spontaneous, as well as induced, cell-specific cytokine production should be measured and evaluated in relation to various disease states.
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PMID:Spontaneous cytokine production and its effect on induced production. 1220 58


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