Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clonal deletion and/or inactivation establishes tolerance to self antigens. Endogenous and exogenous (bacterial) superantigens, like the staphylococcal enterotoxins, induce ligand-specific clonal anergy in vivo and thus are believed to mirror aspects of post-thymic tolerance mechanisms in mature peripheral T cells. Here we analyzed the level of anergy of ligand-responsive V beta 8+ T cells from staphylococcal enterotoxin B (SEB)-primed mice in vivo and in vitro. Upon in vitro restimulation with SEB, CD4+V beta 8+ and CD8+V beta 8+ T cells failed to produce IL-2. However, functional IL-2 receptors were triggered, since supplementation with IL-2 induced clonal growth in virtually all CD4+V beta 8+ and CD8+V beta 8+ T cells as determined by limiting dilution analyses. Thus in vitro unresponsiveness of lymphocytes from SEB-primed mice reflects the inability of SEB-reactive V beta 8+ T cells to produce IL-2. Surprisingly, anergy as defined in vitro was at variance with that in vivo. Following further challenge with SEB, systemic and acute lymphokine production (including IL-2 and tumor necrosis factor) occurred with almost identical peak values and kinetics to primary in vivo responses, and D-galactosamine-sensitized mice succumbed to lethal shock. Polymerase chain reaction analyses revealed that CD4+V beta 8+ expressed IL-2-specific mRNA in vivo upon restimulation with SEB. While lymphokine production and expression of the IL-2 receptor was similar to the response to in vivo primary stimulation, only CD8+V beta 8+ T cells expanded clonally upon reintroduction of SEB in vivo. Hence primed V beta 8+ T cells challenged with SEB display in vitro anergy yet in vivo responsiveness, at least in part. We conclude that the state of anergy is reversible, dependent upon the quality of activation signals provided in in vivo rather than in in vitro culture conditions.
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PMID:Superantigen-reactive T cells that display an anergic phenotype in vitro appear functional in vivo. 771 7

During and after cardiopulmonary bypass (CPB), cytokines may affect cardiac performance and the immune response and are therefore of diagnostic and therapeutic interest. We have used EIA/EASIA kits to measure arterial and venous levels of interleukin-1-beta (IL-1-beta), IL-2, IL-2 receptor (IL-2-R), IL-6, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma in 12 men and 3 women (mean age 59.4 +/- 8.5 years, mean left ventricular ejection fraction 66 +/- 11%, average of 2.5 +/- 0.64 vessels affected by disease) undergoing elective coronary artery bypass grafting (CABG). On average each patient received 3 +/- 0.85 bypass grafts and required a postoperative maximum dopamine-dose of 3.8 micrograms/kg per min. Mean CPB and operation times were 60 +/- 21 min, and 132 +/- 16 min, respectively. During CPB, the venous levels of IL-2 temporarily decreased from 234 to 0 (p < 0.05) pg/ml and arterial and venous levels of IL-2-R temporarily decreased from 28 to 16, and 36 to 18 pM (p < 0.05), respectively. After termination of CPB, there was an increase in the arterial and venous levels of IL-6 from below 3 to 253 and 277 pg/ml (p < 0.05) and TNF-alpha from 1.1 to 5.7 and 0.7 to 4.0 pg/ml, respectively (p < 0.05). Tumor necrosis factor-alpha-increases peaked 30 min, and IL-6 increases peaked 4 h after termination of CPB. Twenty-four hours after the end of CPB, IL-6 showed a tendency to return to baseline, but still remained significantly elevated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Arterial and venous cytokine response to cardiopulmonary bypass for low risk CABG and relation to hemodynamics. 772 42

Toxic shock syndrome (TSS) is a multisystem disorder characterized by fever, hypotension, and involvement of three other organ systems. The etiologic agent is a toxigenic strain of Staphylococcus aureus which secretes the exotoxin, TSST-1. The toxin is a superantigen which stimulates the immune system to produce interleukin-1 (IL-1), interleukin-2, and tumor necrosis factor (TNF). We hypothesized that TSST-1 induces the release of IL-2 which in turn is either directly involved or acts via an additional mediator to produce hypotension. We submitted four pairs of normal anesthetized adult female baboons to intravenous boluses of TSST-1. One baboon in each pair received anti-IL-2 intravenously and anti-IL-2 receptor intrathyroidally 15 min prior to TSST-1. The other baboon received the same dose and placement of anti-sheep red blood cell antibody. Systolic and diastolic blood pressure was recorded continuously and mean arterial pressure was calculated and plotted. IL-1, IL-2, IL-6, and TNF were measured in serum at varying times before and after toxin administration. Systolic, diastolic, and mean arterial pressure were significantly lower in the sham-treated group versus the experimental (anti-IL-2/IL-2R) group (p < .05 for all variables). In addition no differences were seen in any of the measurements between experimentally treated baboons and those receiving no TSST-1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The pathogenesis of experimental toxic shock syndrome: the role of interleukin-2 in the induction of hypotension and release of cytokines. 774 41

Serum levels of 13 different cytokines and receptors were measured serially in 78 patients with aggressive non-Hodgkin's lymphoma (NHL) treated by 4 cycles of an intensive multi-agent chemotherapy regimen. Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered subcutaneously in 36 of these patients from day + 5 to day + 18 after each chemotherapy. Statistically significantly higher pretreatment levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), the soluble IL-2 receptor (sIL-2r), the soluble transferrin receptor (sTf-r), and neopterin, were observed in NHL patients as compared to controls (p < 0.001 for all molecules). sIL-2r and sTf-r levels correlated with tumor burden (p < 0.001 and p = 0.003, respectively) whereas IL-6 was higher in patients presenting B symptoms (p < 0.001). Cytokine levels progressively declined to normal ranges in responding patients, while they remained elevated in non-responders. Relapsed patients also presented increased concentrations of several molecules. During the administration of GM-CSF, we observed the drastic increase of sIL-2r, while lower elevations were recorded for a number of cytokines, including IL-8, tumor necrosis factor-alpha, interleukin-1 beta, IL-6, and IL-2. However, upon completion of the induction treatment, cytokine/receptor levels were comparable among individuals with the same type of response, whether or not they had received GM-CSF. No single parameter was found to be of prognostic significance, but the combination of elevated IL-10 and of sIL-2r greater than 3000 U/ml selected a subgroup of 7 patients who failed induction treatment (p = 0.002). These results demonstrate that cytokine and soluble receptor measurements can provide valuable informations for a better management of NHL, in terms both of markers to monitor disease activity and of prognostic indicators.
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PMID:Clinical implications of cytokine and soluble receptor measurements in patients with newly-diagnosed aggressive non-Hodgkin's lymphoma. 785 83

The immunomodulator ammonium trichloro(dioxyethylene-0-0')tellurate (AS101) has previously been found by us to have radioprotective properties when injected into mice before sublethal and lethal doses of irradiation. AS101 also was found to protect mice from hematopoietic damage caused by various chemotherapeutic drugs. Based on these findings, phase II clinical trials with cancer patients treated with AS101, in combination with chemotherapy, are currently underway. In the present study, we wanted to assess the role of several cytokines in the radioprotection conferred by AS101. We show that the administration of neutralizing antibodies against interleukin-1 (IL-1) receptor, IL-6 receptor, IL-6, tumor necrosis factor (TNF), or stem cell factor (SCF) completely abrogates the ability of AS101 to increase the survival of lethally irradiated mice. Moreover, the injection of each of these antibodies reduces the ability of AS101 to increase the number of BM, spleen cells, and the number of circulating neutrophils, lymphocytes, and platelets in irradiated mice. In addition, these antibodies abrogate the enhancing effect of AS101 on the secretion of IL-3, IL-6, and granulocyte-macrophage colony-stimulating factor, all of which decrease significantly in sublethally irradiated mice. By contrast, the injection of anti-IL-2 receptor antibody or control Igs to AS101-treated mice does not interfere with the radioprotective effects of the compound. These results suggest a role for IL-1, IL-6, TNF alpha, and SCF in the radioprotective effect of AS101. Because cytokine toxicity remains a significant concern, the clinical application of AS101, which has no toxicity, is particularly valuable.
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PMID:Role of endogenous cytokines secretion in radioprotection conferred by the immunomodulator ammonium trichloro(dioxyethylene-0-0')tellurate. 788 74

The construction of an in vitro model allowed an investigation of the basic functions of immunocompetent cells after laser irradiation. Among low-energy laser sources, the helium-neon (He-Ne) laser, with a wavelength of 632.8 nm, has often been found to produce photobiological effects including evidence of interference with immunological functions. Previous experiments revealed an influence of He-Ne laser irradiation on concentrations of interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), and interferon-gamma (IFN-gamma) in supernatants of cultures of human peripheral blood mononuclear cells (PBMC) with increased cytokine concentrations after irradiation of 18.9 J/cm2 and decreased concentrations after irradiation of 37.8 J/cm2. Now, the mechanisms involved were studied. Results showed that cytokine production of cells stimulated with phytohemagglutinin (PHA), concanavalin A (Con A), or bacterial lipopolysaccharide (LPS) was altered significantly after laser irradiation but not after stimulation with staphylococcus aureus enterotoxin B (SEB). In situ hybridization of IFN-gamma mRNA producing PBMC revealed that the number of positive cells was modulated similarly. The results were identical in cultures of enriched monocytes (M phi) or enriched T cells. Cells of the human monocytic cell line Mono Mac 6 were also influenced after LPS stimulation, whereas constitutively IL-2-producing Jurkat cells were not influenced by laser irradiation at any energy density. Analysis of the IL-2 receptor (IL-2R) and intercellular adhesion molecule-1 (ICAM-1) expression in PBMC showed partial down-regulation of both receptors at 37.8 J/cm2, but only after stimulation with PHA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Helium-neon laser irradiation induces effects on cytokine production at the protein and the mRNA level. 790 41

We studied the effect of single or combination of interleukin-2 (IL-2), interleukin-4 (IL-4) and tumor necrosis factor (TNF) on lymphokine-activated killer cells (LAK) activity which killed both of target cells HepG2 and 2 2,1,5 cells induced for seven days. It was shown that LAK activity induced by the combination of triplet of IL-2, IL-4 and TNF was higher than that induced by single or two of IL-2, IL-4 and TNF, and that enhanced LAK activity was associated with the quantity of IL-2 receptor expression and lysosomes of LAK precursors.
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PMID:[The effect of interleukin-2, interleukin-4 and tumor necrosis factor on LAK cells activity]. 792 66

Children with poor prognoses regarding solid tumors have benefited from autologous bone marrow transplantation as a treatment modality. Posttransplantation adjuvant interleukin-2 (IL-2) therapy has previously been shown to improve prognosis in adults with neoplastic disease. The improved survival probability has been attributed to IL-2-mediated stimulation of the immune system and its antineoplastic activity. In this study, 10 pediatric patients with solid tumors in complete remission after autologous stem cell transplantation were treated with recombinant IL-2, which was administered in three 5-day cycles of continuous intravenous infusions with a 2-week rest in between cycles. We demonstrated that IL-2 therapy enhanced transplantation-related stimulation of the immune system, on both the cellular and humoral levels. Peripheral blood T and natural killer (NK) cells increased by the factors four and 14, respectively. Activation of the immune system was demonstrated by significantly elevated levels of soluble IL-2 receptor (IL-2R) and increased CD25 surface expression on T lymphocytes. IL-2 also induced significant proliferation of the CD56bright NK-cell subpopulation that appears post-bone marrow transplant (BMT) and is found only in minimal amounts in normal controls. In vivo and in vitro production of tumor cytotoxic cytokines tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) was significantly stimulated following IL-2 therapy, further indicating IL-2-mediated stimulation of the antineoplastic activity of the immune system.
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PMID:Induction of two distinct natural killer-cell populations, activated T cells and antineoplastic cytokines, by interleukin-2 therapy in children with solid tumors. 792 75

This study evaluates the plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and soluble IL-2 receptor (sIL-2R) in cancer patients infused with radiolabelled murine monoclonal antibodies (MAbs) for the purpose of imaging and dosimetry. Blood samples were collected from 13 patients (10 with colon cancer and 3 with lung cancer) before and at 4 and 7 days after infusion of either conventional intact 111In-MAb or a bifunctional antibody delivery system. For all subjects, except one, this was the first exposure to murine MAb. Before infusion, higher levels of TNF-alpha, IL-1 beta, and sIL-2R than the average expected in the plasma of healthy individuals were found. A significant decrease was noted in TNF-alpha when preinfusion concentrations were compared to 4 day (P < 0.01) or to 7 day (P < 0.05) postinfusion values. A 50% or greater decrease in IL-1 beta was also observed in most individuals with time after infusion. In contrast, sIL-2R concentrations remained relatively stable during the 1 week follow-up period. However, strikingly different patterns in the IL-1 beta and sIL-2R levels were noted in the subject who had received two previous murine antibody infusions. Our data show that the administration of radiolabelled murine antibodies, either conventional or bifunctional, can significantly alter plasma levels of TNF-alpha and IL-1 beta. These cytokines are important in immunoregulation and, perhaps also, in modulation of neoplastic growth.
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PMID:Effects of radiolabelled murine antibody infusion on TNF-alpha, IL-1 beta, and soluble IL-2 receptor in cancer patients. 793 17

Leukocytic cytokines are produced by cells of the immune system and are prominent regulators of the immune response and in some cases various systemic responses. Leukocytic cytokines are released during immune responses and may act in autocrine, paracrine, or endocrine manners. Although over a dozen avian leukocytic cytokines have been described based on functional activities, characterization at the molecular level is not well developed. Two exceptions are 1) myelomonocytic growth factor, a colony-stimulating factor-like cytokine required for the growth and differentiation of hematopoietic precursor cells, particularly myelomonocytic cells; and 2) the avian transforming growth factor-beta (TGF-beta) family of cytokines, which modulate wound healing, bone metabolism, and cellular differentiation. Cytokines with bioactivities similar to mammalian interleukin (IL)-1, IL-2, IL-6, and interferon-gamma have been at least partially purified. Cytokines with bioactivities similar to mammalian IL-8, colony-stimulating factor, and tumor necrosis factor-alpha have been reported but are not well characterized at the molecular level. With a few exceptions, including TGF-beta and thymulin, highly purified leukocytic cytokines of mammalian origin have diminished or no specific activity in avian assay systems. The chicken IL-1 receptor has been cloned and the predicted amino acid sequence shares 60% homology with the human IL-1 receptor. A component of the chicken IL-2 receptor has been partially purified but little is known about other avian leukocytic cytokine receptors. Potential applications of leukocytic cytokines in poultry production originate from their regulation of a variety of functions such as disease resistance, would healing, bone accretion, nutrient partitioning, appetite, growth, and reproduction.
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PMID:Avian leukocytic cytokines. 793 64


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