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

The popliteal lymph node (PLN) assay has been proposed to predict the 'autoimmunogenic' potential of xenobiotics. A better understanding of the processes involved in PLN responses is needed to establish the value of this assay for preclinical safety evaluation. In order to determine whether PLN responses involve CD4(+) or CD8(+) T-cells, the effects of streptozotocin (STZ), a prototypic immunotoxic compound, were analyzed after injection into the hind footpad of C57 BL/6 mice and major histocompatibility complex (MHC) class I or II deficient mice. The involvement of type 1 or type 2 cell control on the production of cytokine mRNAs was analyzed in lymph node cells by quantitative RT-PCR, together with the analysis of a wide range of cytokine mRNAs after STZ injection (IL-1alpha, IL-1beta, TNF-alpha, IFN-gamma, IL-2, IL-2 receptor, IL-4, IL-5, IL-6, IL-10 and IL-12). We have found that mice depleted in CD8(+) T-cells did not respond to STZ, whereas mice depleted in CD4(+) T-cells exhibited the expected positive PLN responses, with increased weight and cellularity indices. STZ induced a low production of interleukin (IL)-2 mRNAs, a mild increase in IL-1alpha and IL-6 mRNAs production, and a dramatic increase in IFN-gamma, IL-1beta, TNF-alpha, IL-12 and IL-2 receptor mRNAs, which correlated with positive PLN responses. No effects on IL-4, IL-5 and IL-10 mRNAs synthesis were noted. In CD8(+) T-cell deficient mice, there was no production of IFN-gamma or IL-6 mRNAs. These results suggest that PLN responses to STZ are under the control of type 1, MHC class-I-restricted, CD8(+) T-cells. This is in accordance to the known physiopathology of STZ-induced diabetes. Additional studies are necessary to establish the mechanism of CD8+ T-cell activation.
 ...
PMID:The popliteal lymph node response to streptozotocin is under type 1, MHC class-I restricted, CD8(+) T-cell control. 1077 64

Evaluation of cytokine gene expression following in vitro stimulation is one means of examining the dysregulation of the immune system in human immunodeficiency virus (HIV) infection. We have assessed differences in the immune status of non-HIV-infected (HIV-) and HIV-infected (HIV+) individuals by evaluating the kinetics of the expression of cytokine genes. We compared detailed time courses of cytokine mRNA expression in HIV- and HIV+ peripheral blood mononuclear cells (PBMC) and found that there is a significant shift (P<0.01) for all cytokines examined (interleukin 2 [IL-2], IL-6, IL-10, gamma interferon, and tumor necrosis factor alpha [TNF-alpha]) to an earlier time of mean peak mRNA expression by HIV+ PBMC (between 4 and 8 h) compared to HIV- PBMC (8 h) in response to either phytohemagglutinin (PHA) or anti-CD3 stimulation. Additional studies showed that although PHA-stimulated HIV+ PBMC showed decreased median IL-2, IL-4, and TNF-alpha mRNA levels, they typically demonstrated more rapid kinetics (increased mean 4-h/24-h cytokine mRNA ratios), with significant differences for IL-4 (P<0.05) and TNF-alpha (P<0.005), compared to HIV- PBMC. The use of fresh or frozen cells gave comparable cytokine mRNA data; however, the secretion of some cytokine proteins (IL-2 receptor, IL-10, and TNF-alpha) appeared to be reduced in HIV+ PBMC that had been frozen and thawed. Our studies demonstrate that the kinetics of cytokine gene expression can reveal additional dysregulation of the immune system in HIV infection, suggesting that PBMC of HIV-infected persons exist in an activated state in vivo that permits them to express cytokine genes more rapidly than a normal PBMC.
 ...
PMID:Cytokine gene expression occurs more rapidly in stimulated peripheral blood mononuclear cells from human immunodeficiency virus-infected persons. 1097 52

We studied the effects of the immunosuppressant sodium fusidate (fusidin) on murine immunoinflammatory diabetes mellitus (DM) induced by multiple low doses of streptozotocin (SZ). Fusidin was given by gavage to three strains of mice (C57KsJ, C57BL/6, CD1) at doses 10 or 100 mg/kg body weight every other day. The drug was administered as an early or late prophylactic regime starting either 1 day prior to the first or after the fifth and last injection of SZ. In both situations the largest dose of fusidin successfully reduced the clinical, chemical and histological signs of DM, the treated mice having significantly lower glycaemic values and milder (often absent) insulitis compared with sham-treated animals or controls given SZ alone. The antidiabetogenic effect was long-lasting as it was maintained up to 1 month after cessation of therapy. In contrast, fusidin prophylaxis failed to prevent development of hyperglycaemia acutely induced by one single and high (160 mg/kg) dose of SZ, which is a model of DM primarily due to the toxic action of SZ on the beta cells and does not involve immunopathogenetic mechanisms. On day 14 after SZ, fusidin markedly altered the circulating cytokine profile induced in vivo by ConA, reducing the levels of IFN-gamma, IL-2 and TNF-alpha and augmenting the level of IL-6. However, only the inhibitory effect of the drug on the synthesis/release of IFN-gamma seemed to be causally related to its capacity to counteract the SZ-induced DM. In fact, the disease was prevented by a neutralizing monoclonal antibody (mAb) against IFN-gamma, but not by anti-IL-2 receptor mAb, a soluble form of TNF-receptor type 1 or recombinant human IL-6. The prevention of disease by fusidin was also partly reversed by exogenously administered recombinant mouse IFN-gamma. The data provide further in-vivo evidence for the anti-diabetogenic and immunomodulatory properties of fusidin and indicate that this drug could have a role in prevention and treatment of human type 1 DM.
 ...
PMID:Sodium fusidate ameliorates the course of diabetes induced in mice by multiple low doses of streptozotocin. 1109 Feb 38

After adoptive transfer of pre-activated lymphocytes into the operation cavity of glioma patients, tumor regression and improved survival have been reported in some patients. Results were most impressive when bispecific antibodies with tumor x CD3 specificity were also applied. In this study, we attempted to avoid time-consuming pre-activation procedures for adoptively transferred cells by using a combination of bispecific antibodies directed to the EGF receptor (EGFR) on tumor cells and to CD3 and CD28 on T cells. Eleven patients with high-grade malignant glioma received 3 injections of 2 bispecific antibody fragments (EGFR x CD3 and EGFR x CD28) together with freshly isolated autologous lymphocytes via an Ommaya reservoir. Intracavitary fluid aspirated during immunotherapy was examined for markers of T-cell activation. Increased levels of soluble IL-2 receptor and TNF-alpha were detected in the intracavitary fluid of all patients tested. Two of the 11 treated patients experienced a beneficial response to therapy as defined by a transient contrast enhancement in subsequent MRI scans and prolonged survival. Side effects were transient and consisted of fever, nausea, headache and aggravation of pre-existing neurologic deficits. These adverse effects were most likely due to the antibody construct containing anti-CD3 specificity. Two patients developed cerebral edema and required steroid treatment.
 ...
PMID:Local immunotherapy of glioma patients with a combination of 2 bispecific antibody fragments and resting autologous lymphocytes: evidence for in situ t-cell activation and therapeutic efficacy. 1114 49

Malignant lymphoma is a major cause of hemophagocytic syndrome (HPS), in which reactive macrophages, phagocytic red blood cells, white blood cells, and platelets proliferate in bone marrow, liver, and spleen. In contrast to T/NK-cell lymphoma-associated hemophagocytic syndrome (T/NK-LAHS), few cases of B-LAHS have been reported; thus, the clinical characterization of B-LAHS remains to be established. We describe here four cases of B-LAHS that include the following features: (1) HPS was the initial presentation; (2) bone marrow involvement with large-cell lymphomas was noted in all cases, despite lack of remarkable lymphadenopathy; (3) no active infection with Epstein-Barr virus as the etiological agent was confirmed; (4) except for the spleen in one case, primary site of lymphoma could not be determined; and (5) serum IL-6, soluble IL-2 receptor, and IFN-gamma- but not TNF-alpha and IL-1 beta-, were significantly elevated. Such characteristics are peculiar to and different from those usually seen in B-cell lymphoma, suggesting that B-LAHS is a unique clinical entity among B-cell lymphomas.
 ...
PMID:[Clinical characterization of B cell lymphoma-associated hemophagocytic syndrome]. 1115 15

CD7 and CD28 are Ig superfamily molecules expressed on thymocytes and mature T cells that share common signaling 0mechanisms and are co-mitogens for T cell activation. CD7-deficient mice are resistant to lipopolysaccharide (LPS)-induced shock syndrome, and have diminished in vivo LPS-triggered IFN-gamma and tumor necrosis factor (TNF)-alpha production. CD28-deficient mice have decreased serum Ig levels, defective IgG isotype switching, decreased T cell IL-2 production and are resistant to Staphylococcus aureus enterotoxin-induced shock. To determine synergistic roles CD7 and CD28 might play in thymocyte development and function, we have generated and characterized CD7/CD28 double-deficient mice. CD7/CD28-deficient mice were healthy, reproduced normally, had normal numbers of thymocyte subsets and had normal thymus histology. Anti-CD3 mAb induced similar levels of apoptosis in CD7-deficient, CD28-deficient and CD7/CD28 double-deficient thymocytes as in control C57BL/6 mice (P = NS). Similarly, thymocyte viability, apoptosis and necrosis following ionomycin or dexamethasone treatment were the same in control, CD7-deficient, CD28-deficient and CD7/CD28-deficient mice. CD28-deficient and CD7/CD28-deficient thymocytes had decreased [3H]thymidine incorporation responses to concanavalin A (Con A) stimulation compared to control mice (P < or = 0.01 and P < or = 0.05 respectively). CD7/CD28 double-deficient mice had significantly reduced numbers of B7-1/B7-2 double-positive cells compared to freshly isolated wild-type, CD7-deficient and CD28-deficient thymocytes. Con A-stimulated CD4/CD8 double-negative (DN) thymocytes from CD7/CD28 double-deficient mice expressed significantly lower levels of CD25 when compared to CD4/CD8 DN thymocytes from wild-type, CD7-deficient and CD28-deficient mice (P < 0.05). Anti-CD3-triggered CD7/CD28-deficient thymocytes also had decreased IFN-gamma and TNF-alpha production compared to C57BL/6 control, CD7-deficient and CD28-deficient mice (P < or = 0.05). Thus, CD7 and CD28 deficiencies combined to produce abnormalities in the absolute number of B7-1/B7-2-expressing cells in the thymus, thymocyte IL-2 receptor expression and CD3-triggered cytokine production.
 ...
PMID:Comparison of thymocyte development and cytokine production in CD7-deficient, CD28-deficient and CD7/CD28 double-deficient mice. 1115 49

There are a number of investigations which indicate the important relationship between depression and cytokines. In this study, we investigated plasma interleukin (IL)-1beta, IL-6, soluble IL-2 receptor (sIL-2R) and tumor necrosis factor (TNF)-alpha of depressed patients whose clinical evaluation was performed by the Hamilton Rating Scale for Depression (HAM-D) and the Profile of Mood States (POMS). They were compared with those of the control subjects, and before and after treatment with antidepressants. Before the treatment, plasma IL-1beta, IL-6, sIL-2R and TNF-alpha of the patients were not significantly different from those of the control subjects. sIL-2R was positively correlated with the POMS-tension-anxiety subscale and tended to have a positive correlation with HAM-D. After pharmacotherapy, TNF-alpha levels of the depressed patients increased, without any relationship between the change in the HAM-D or the POMS and the change in TNF-alpha. These results suggest that the plasma sIL-2R concentration is associated with mood state, and that the plasma TNF-alpha concentration is increased after pharmacotherapy in Japanese depressed patients.
 ...
PMID:Plasma concentrations of interleukin-1beta, interleukin-6, soluble interleukin-2 receptor and tumor necrosis factor alpha of depressed patients in Japan. 1117 46

We investigated the effects of drugs, especially anti-pulmonary disease agents, on the production of cytokines from human peripheral blood mononuclear cells (PBMC). Roxithromycin (RXM), a macrolide antibiotic with the structure of 14-member macrocycline ring increased adherent cells (monocyte/macrophages), whereas it suppressed the proliferation of PBMC stimulated with phytohemagglutinin (PHA). RXM suppressed the production of IL-1 beta and TNF-alpha from lipopolysaccharide (LPS)-stimulated PBMC in a dose-dependent manner. Levofloxacin, a fluorinated quinolone, increased IL-2 production by PBMC stimulated with PHA. The production of GM-CSF and soluble IL-2 receptor was suppressed at high concentrations of LVFX. LVFX suppressed IL-1 beta production, but did not the production of TNF-alpha and IL-8 production. A beta-adrenoceptor agonists (beta-agonist), procaterol, clenbuterol, fenoterol and terbutaline suppressed the production of TNF- and IL-1 beta. TNF-alpha production was almost completely suppressed by dibutyryl cyclic AMP (dbcAMP), whereas IL-1 beta production appeared to be partially refractory even at the highest concentration examined. Both procaterol and theophylline elevated cAMP levels in LPS-stimulated PBMC, but the effect of procaterol was limited. The inhibition of the production of TNF-alpha and IL-1 beta by procaterol was additively potentiated with theophylline. Of examined phosphodiesterase (PDE) isozyme inhibitors type IV PDE inhibitors were more effective in inhibiting the production of TNF-alpha and IL-1 beta by LPS-stimulated PBMC than a nonselective, type III or type III/IV inhibitor. The addition of the beta-agonist increased the inhibitory effect of tested PDE inhibitors on the production of TNF-alpha and IL-1 beta Type IV, type III and nonselective PDE inhibitors were effective in inhibiting the production of IFN-gamma and IL-2 in a dose-dependent manner. In contrast, the production of IL-4 and IL-5 was inhibited by only the highest concentration of type IV inhibitor, and other agents had no effect on the production. Similarly, dbcAMP inhibited the production of IFN-gamma and IL-2 more potently than that of IL-4 and IL-5. The addition of the beta-agonist increased the inhibitory effect of tested PDE inhibitors on the production of IFN-gamma and IL-2 production. These findings indicate that these agents have an immunodulatory action on the production of cytokines by PBMC and also indicate that they could be potent pharmacological agents for the treatment of diseases in which several cytokines are important etiological factors.
 ...
PMID:[Modulation of cytokine production from human mononuclear cells by several agents]. 1119 79

The complication of hypercalcemia is reported to occur only in 2.5-4.8% of patients with acute lymphoblastic leukemia (ALL). We herein report a 53-year-old female patient with early B-cell ALL, complicated with extreme hypercalcemia (15.2 mg/dL). Bone X-ray revealed osteolytic changes in many locations. Serum 1,25(OH)2vitaminD3 and parathyroid hormone (PTH) levels were suppressed below normal ranges on admission. The circulating parathyroid hormone-related protein (PTHrP) value was within a normal range (< 1.1 pmol/L). Serum concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and soluble IL-2 receptor were increased to 72 pg/ml, 25.3 pg/ml, and 1469 U/ml, respectively. Following the induction chemotherapy, the serum calcium level was promptly normalized accompanied with decreases in serum TNF-alpha, IL-6 and soluble IL-2 receptor values to 34 pg/ml, 6.35 pg/ml, and 737 U/ml, respectively. Serum PTHrP values remained within detectable levels. To our knowledge, this is the first case of B-cell ALL in a patient who developed hypercalcemia with elevated concentrations of TNF-alpha, IL-6, and soluble IL-2 receptor, but not related to PTHrP. High circulating proinflammatory cytokines may have contributed to development of ALL-induced osteolysis and hypercalcemia in the present case.
 ...
PMID:Hypercalcemia in a patient with B-cell acute lymphoblastic leukemia: a role of proinflammatory cytokine. 1152 24

In cultures, and in tissues as well, Hodgkin's and Reed-Sternberg (H-RS) cells and anaplastic large cell lymphoma (ALCL) cells are known to express a variety of cytokines, including IL-1, -5, -6, -8, -9, TNF-alpha, GM-CSF, M-CSF, TGF-beta, CD70, CD80, and CD86. Various numbers of H-RS/ALCL cells may express cytokine receptors (R), such as CD30, CD40, IL-2R (CD25/CD122), IL-6R (CD126), IL-7R (CD127), TNF-R (CD120), TGF-beta-R (CD 105/endoglin), M-CSF-R (CD115), and SCF-R (CD117/c-kit receptor). All of these cytokines and cytokine receptors are implicated in the growth regulation of H-RS/ALCL cells, the histopathologic alterations in tissues, and the clinical manifestations in patients with Hodgkin's disease (HD) or ALCL. Many of these cytokines or cytokine receptors also play an important role in the pathogenesis of other types of lymphomas. In this review, we describe the cytokine or cytokine-receptor expression that is diacritic for H-RS/ALCL cells. The identification of such unique cytokine-cytokine receptor interactions is likely to explain the biologic property that distinguishes HD/ALCL from other types of lymphomas. These interactions include those of CD30L-CD30, CD40L-CD40, CD70-CD27, CD80/CD86- CD28, SCF-CD117, IL-9-IL-9R, and IL-7-IL-7R. The H-RS/ALCL cells express IL-9 and two cytokine receptors, CD30 and CD117, which are observed infrequently in NHLs. Although IL-7 expression is not restricted to H-RS/ALCL cells, the expression of IL-7 in conjunction with IL-9 and/or CD117 may be regarded as unique for HD/ALCL because of an unusual combination and a synergistic activity among these cytokines. The expression of CD70 and CD80/CD86 (as cytokines) may exert a unique effect in HD because of intimate contact between H-RS cells and CD27/CD28-positive T cells. The expression of these costimulators (CD70 and CD80/CD86) and other adhesion/constimulator molecules such as CD54 and CD58, along with the secretion of soluble cytokines such as IL-1, IL-6, IL-7, or TNFs by H-RS/ALCL cells, could result in the profound T-cell proliferation often seen in lymph nodes involved by HD and some ALCL. On the other hand, the expression of CD30L and CD40L by surrounding T cells may affect the proliferation of H-RS/ALCL cells. The cytokine-cytokine receptor interaction between H-RS cells and T cells via direct cell-cell contact is bidirectional, a situation not commonly seen in NHLs. Copyright 1995 S. Karger AG, Basel
 ...
PMID:Hodgkin's Disease and Anaplastic Large Cell Lymphoma Revisited. 1. unique cytokine and cytokine receptor profile distinguished from that of non-hodgkin's lymphomas. 1172 67


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>