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)

This work was designed to study the proliferative response of tumor-associated lymphocytes (TAL) from neoplastic effusions against autologous tumor cells and the immunophenotype pattern of TAL from neoplastic effusions and that of PBMC of the same patients. We also compared the serum levels of the cytokines interleukin (IL) 1 beta, 2 and 6, tumor necrosis factor-alpha (TNF alpha) and soluble IL-2 receptor (sIL-2R) with those present in neoplastic effusions of the same patients. Moreover, we examined the ability of TAL and peripheral blood mononuclear cells (PBMC) to produce and release the cytokines and sIL-2R and to express membrane CD25 following their stimulation with phytohemagglutinin (PHA) in vitro. Finally, we compared the cytokines/sIL-2R production and membrane CD25 expression by PHA-stimulated PBMC of the patients with neoplastic effusions with a series of 90 cancer patients without neoplastic effusions and 20 normal healthy subjects. Thirteen neoplastic pleural and eight peritoneal effusions were collected from 11 patients with primary lung cancer, 7 with primary epithelial ovarian cancer, 1 with breast cancer, 1 with pleural mesothelioma, and 1 with pancreatic cancer. The proliferative response of TAL from neoplastic effusions against autologous tumor cells was lower than the response to PHA, IL-2, and anti-CD3, but significant. The percentage distribution of CD3+ and CD8+ lymphocyte subpopulations was higher in peritoneal than in pleural effusions, while the CD16+ subset was higher in pleural than in peritoneal effusions. The percentage distribution of CD16+ was significantly lower in pleural effusions than in PBMC of patients with pleural effusions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumor-associated lymphocytes (TAL) are competent to produce higher levels of cytokines in neoplastic pleural and peritoneal effusions than those found in sera and are able to release into culture higher levels of IL-2 and IL-6 than those released by PBMC. 852 43

Serum cytokine profiles, T-cell subsets, and general parameters of immune activation were evaluated in 15 patients with acute primary HIV-1 infection, and compared with those obtained from 18 patients with acute primary Epstein-Barr virus (EBV) infection and from 18 control subjects in order to elucidate possible defects of immune response to HIV in early phases of virus-host interaction. Mean CD4+ cell count, serum concentrations of interleukin (IL)-2, IL-4, soluble IL-2 receptor (sIL-2R), tumor necrosis factor (TNF)-alpha, 5'-neopterin, and beta 2-microglobulin were significantly lower in acute HIV-1 infection than in EBV infection. Both acute HIV-1 and EBV infections were characterized by significantly higher mean CD8+ cell count and soluble CD8 antigen (sCD8) levels compared to control subjects, while acute HIV-1 infection was accompanied by the highest interferon (IFN)-gamma serum concentrations. In primary HIV-1 infection, significant impairment of CD4+- mediated T-helper function may lead to viral escape and persistence of infection despite an early and vigorous CD8+ T-lymphocyte activation.
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PMID:Serum cytokine profiles in acute primary HIV-1 infection and in infectious mononucleosis. 859 86

The outcome of immune responses can be predicted by the lymphokine production pattern of the participating cells. Cytokines of the T helper type 1 (Th1) cells mediate inflammatory responses and delayed-type hypersensitivity (DTH), whereas Th2-like T cells predominantly produce cytokines, which stimulate antibody production by B cells. Immunoregulatory therapy of autoimmune diseases with unknown antigens may be achieved by inhibiting the production of inflammatory cytokines and induction of protective cytokines of Th2-like T cells. To determine the immunoregulatory capacity of the phosphodiesterase inhibitor pentoxifylline (PTX), which is known to suppress the production of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), this drug was used in mitogen and antigen-stimulated lymphocyte cultures as well as in patients with multiple sclerosis. PTX significantly decreased TNF-alpha and interleukin-12 (IL-12), whereas it increased IL-4 and IL-10 production. In addition, PTX inhibited cell proliferation, which was associated with a marked reduction in CD25 (IL-2 receptor alpha-chain) and CD54 (intercellular adhesion molecule-1; ICAM-1) expression. Increasing doses of PTX significantly reduced TNF-alpha and IL-12 mRNA expression of blood mononuclear cells, but increased IL-4 and IL-10 expression in eight patients with relapsing-remitting multiple sclerosis. These results indicate that PTX modulates immune reactions favouring a Th2-like response and may therefore be useful for the treatment of autoimmune diseases with a dominant Th1-like T cell response.
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PMID:Pentoxifylline, a phosphodiesterase inhibitor, induces immune deviation in patients with multiple sclerosis. 863 62

We previously reported the generation and characterization of a panel of CD4(+) autoreactive T cell clones that suppress development of autoimmune diabetes in non-obese diabetic (NOD) mice. We showed that the protective capacity of the T cell clones correlated with secretion of an activity that potently inhibits allogeneic mixed lymphocyte reaction (allo-MLR). In this report, we describe the biological characteristics of the allo-MLR inhibitory activity (MLR-IA, short for mixed lymphocyte reaction inhibitory activity) secreted by the protective T cell clone, NOD-5. MLR-IA has little effect on initiation of proliferation in an allo-MLR, but it potently inhibits the maintenance and amplification of the proliferative response. MLR-IA is also capable of inhibiting concanavalin A (Con A) stimulated splenic responder T cell proliferation. MLR-IA is reversible in vitro and is not restricted by MHC class I or II proteins. MLR-IA does not affect IL-2 receptor expression of responding T cells and has no effect on IL-2-dependent proliferation of CTLL-20 T cells. Partially purified MLR-IA inhibits IL-2 production in a primary allo-MLR, and decreases IFN-gamma production during secondary allo-MLR and Con A activation, whereas it enhances IL-4 production in both primary and secondary Con A activation. MLR-IA is not neutralized by combination of antibodies specific for transforming growth factor-beta, IL-10, tumor necrosis factor-alpha/beta or IFN-gamma, suggestive of a novel activity. MLR-IA is ammonium sulfate precipitable, sensitive to protease digestion and is destroyed by boiling, indicating that a protein moiety is part of its active structure. Our work suggests that a potentially novel immunoregulatory activity, capable of inhibiting T lymphocyte proliferation and IFN-gamma production, and stimulating IL-4 production, may regulate development of autoimmune diabetes in NOD mice.
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PMID:Biological characteristics of an immunoregulatory activity secreted by an autoreactive CD4+ T cell clone that suppresses autoimmune diabetes in non-obese diabetic mice. 867 56

Interleukin-15 (IL-15) is a novel cytokine that has recently been cloned and expressed. IL-15 interacts with components of the IL-2 receptor and exhibits T-cell stimulating activity similar to that of IL-2. In the present study, we investigated the expression of IL-15 in enriched cultures of human fetal astrocytes and microglia using reverse transcription-polymerase chain reaction (RT-PCR) and immunodetection analysis. Low levels of IL-15 were expressed by unstimulated human fetal astrocytes and microglia, and treatment of astrocytes with interleukin-1 beta (IL-1 beta), interferon-gamma (IFN-gamma), or tumor necrosis factor-alpha (TNF-alpha) increased the expression of IL-15 at both the mRNA and protein level. Treatment of microglia with IFN-gamma and lipopolysaccharide (LPS) similarly increased IL-15 expression in microglia. These findings suggest that IL-15 produced by human fetal astrocytes and microglia may have a role in T cell-mediated immune responses in the human CNS.
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PMID:Interleukin-15 gene expression in human astrocytes and microglia in culture. 880 52

To determine whether the liver plays an immunological role in certain extrahepatic disorders, we investigated the expression of interleukin (IL)-1 beta, IL-6, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha in 11 patients who had recovered from cholecystolithiasis, 12 patients with gastric cancer, 20 patients with chronic hepatitis, and 6 healthy controls. Cytokine mRNAs in the liver were detected by semiquantitative reverse transcribed-polymerase chain reaction. Serum cytokines and soluble IL-2 receptor (sIL-2R) were investigated by enzyme-linked immunosorbent assays. Increases in TNF-alpha, IL-6, IL-1 beta, and IFN-gamma mRNAs were found in the livers of patients with extrahepatic diseases. TNF-alpha and IL-6 peptides were increased in the sera of patients with gastric cancer. TNF-alpha in the sera and TNF-alpha mRNA in the liver were correlated in gastric cancer patients. Surprisingly, sIL-2R in the serum of gastric cancer patients was significantly higher than the level in healthy controls. Our findings suggest that the liver produces cytokines in reaction to extrahepatic lesions. Further, the increase in sIL-2R in gastric cancer patients indicates that malignancy may affect the immune network in vivo.
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PMID:Increased expression of cytokines in liver and serum in patients with extrahepatic diseases. 884 75

The synthetic polynucleotide polyadenylic-polyuridylic acid (polyA:polyU) has shown antitumor activity in murine studies and human breast cancer. PolyA:polyU was evaluated in 25 cancer patients receiving weekly intravenous doses between 3 and 600 mg/m2. PolyA:polyU was well tolerated up to 600 mg/m2, with no doselimiting toxicity (all < grade 3). Side effects included mild elevation in temperature, fatigue, and mild hyperglycemia. No changes outside of the normal range in hematocrit, WBC count, platelet count, total bilirubin, or alkaline phosphatase were observed. Of 25 patients, 18 completed at least one cycle of 6 weeks, and 5 completed two cycles (median 6 weeks). Four patients had stable disease over 11-13 weeks of treatment, and no clinical responses were observed. At 24 h after the first treatment, there were no significant increases in biologic response (beta 2-microglobulin and neopterin in serum, or 2',5'-oligoadenylate synthetase in peripheral blood mononuclear cells). A small increase in beta 2-microglobulin was observed 24 h after the week 3 treatment (1.1-fold, p < 0.01). By the third week of treatment, 2-5A synthetase levels decreased slightly (to 80% of baseline, p < 0.01). No changes in cytokines IL-6, IL-12, tumor necrosis factor (TNF), or IL-2 receptor in serum were detected after 24 h of treatment. Thus, at these doses, polyA:polyU had no marked modulation on biologic responses in vivo, although this preparation significantly induced 2-5A synthetase in peripheral blood mononuclear cells in vitro. PolyA:polyU was well tolerated. An MTD was not reached but was greater than 600 mg/m2 on this weekly schedule.
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PMID:Phase I/IB study of polyadenylic-polyuridylic acid in patients with advanced malignancies: clinical and biologic effects. 887 34

The objective was to investigate if the presence of the v-Ha-ras oncogene could induce immune changes different to the ones observed in normal mice. Therefore, we decided to use Oncomice, the transgenic mice with an activated v-Ha-ras oncogene under the control of the mouse mammary tumor virus-promoter, and their normal inbred counterparts, FVB mice. Both strains of mice were fed the Lieber-DeCarli liquid diet with ethanol or the isocaloric control diet and were injected daily with cocaine or saline. The percentage and absolute number of T and B lymphocytes in the spleen and thymus were determined. The in vitro production of TNF-alpha (tumor necrosis factor-alpha), IL-2 (interleukin-2) and IFN-gamma (interferon-gamma) by spleen cells, and the levels of serum sIL-2R (soluble IL-2 receptor) were also measured. Oncomice fed the Lieber-DeCarli ethanol diet or receiving either saline or cocaine injections presented a higher tumor incidence than Oncomice receiving the control diet. A reduced total number of thymocytes as well as absolute number of cells in all the subsets was found in Oncomice. Moreover, a decreased percentage of CD8+ cells was also observed in Oncomouse spleens. These features were even more marked in ethanol-treated Oncomice. Higher serum sIL-2R levels were observed in Oncomice, especially in mice treated with ethanol or cocaine. The results suggest that the oncogene product, P21ras, plays an important role in dysregulating the immune system and hence in favoring tumorigenesis.
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PMID:Effect of ethanol and cocaine treatment of the immune system of v-Ha-ras-transgenic mice. 889 4

The regulation of human natural killer (NK) cell activation is under the control of a network of regulatory signals provided by cytokines. In the present study, we investigated the functional interaction between interleukin (IL)-4 and two monocyte/macrophage-derived cytokines, IL-12 and IL-15, during the process of NK stimulation. Using freshly isolated human NK cells, we have demonstrated that IL-4 negatively regulates lymphokine-activated killer (LAK) activity induced by IL-15 against the NK-resistant Daudi target cells. In contrast, IL-4 had no effect on IL-12-stimulated LAK generation. The differential effect of IL-4 on NK cell activation by IL-12 and IL-15 correlates with its ability to increase or to down-regulate the level of tumor necrosis factor-alpha and interferon-gamma release by NK cells, respectively. In contrast, endogenous transforming growth factor-beta 1 does not appear to be involved in the IL-4 regulatory pathway. Furthermore, while IL-4 was found to decrease the basal expression of the IL-2 receptor beta subunit utilized by IL-15, it had no effect on the expression of the beta 1 chain of the IL-12 receptor compared to untreated cells. Northern blot analysis indicated that the IL-4 regulatory effect on NK lytic function was associated with its capacity to down-regulate granzyme B and perforin gene transcription in response to IL-15 and its failure to affect the expression of both gene's in response to IL-12. Together, these data suggest the existence of a distinct cross-talk between IL-4 and IL-15 or IL-12 signaling pathways during the regulation of human non-major histocompatibility complex-restricted cytotoxicity.
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PMID:Differential regulation of interleukin-12- and interleukin-15-induced natural killer cell activation by interleukin-4. 892 63

Levofloxacin (LVFX), the bacteriologically active isomer of ofloxacin, is a fluorinated quinolone. LVFX suppressed the proliferative activity of peripheral blood mononuclear cells (PBMC) stimulated with phytohemagglutinin (PHA). LVFX increased interleukin-2 (IL-2) production by PBMC stimulated with PHA in a dose-dependent manner, with more than 10 micrograms/ml of LVFX causing a significant increase. The granulocyte-macrophage colony-stimulating factor and soluble IL-2 receptor production by PHA-stimulated PBMC was suppressed at high concentrations of LVFX. Interleukin-1 beta production by lipopolysaccharide-stimulated PBMC was suppressed in a concentration-dependent manner by LVFX, and tumor necrosis factor-alpha production was suppressed at only the highest concentration. In contrast, interleukin-8 production was little affected by LVFX. These results show that LVFX has an immunomodulatory action on cytokines production by PBMC independent of its antimicrobial activity.
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PMID:Immunomodulatory action of levofloxacin on cytokine production by human peripheral blood mononuclear cells. 895 81


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