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)

A possible correlation between the pathogenicity of autoimmune T cells and their lymphokine production, expression of functional adhesion molecules and expression of some surface antigens was examined. We used four retinal antigen-specific Lewis rat T cell lines and sublines: one specific to the major pathogenic epitope of the human retinal soluble antigen (S-Ag; residues 337-356), and three specific to the major pathogenic epitope of the bovine interphotoreceptor retinoid binding protein (IRBP; residues 1177-1191). The lines have different degrees of uveitogenicity, from highly pathogenic to nonpathogenic. All four T cell lines produced roughly equivalent amounts of interferon-gamma, lymphotoxin/tumor necrosis factor (TNF alpha/beta), interleukin-3, interleukin-6 and transforming growth factor-beta. Interleukin-4 activity could not be detected. The lines also expressed similar levels of functional adhesion molecules, as measured by binding to cultured rat aorta endothelial cells. The nonpathogenic subline, however, was the lowest responder to antigenic stimulation with respect to proliferation and interleukin-2 production. Examination of cell surface antigens showed that in contrast to the other lines, the majority of cells in the nonpathogenic subline lacked detectable expression of CD4. No difference was found in the level of expression of the IL-2 receptor and T cell antigen receptor among the four lines. Because CD4 is the restricting element in these lines, reduced CD4 expression in the nonpathogenic subline may at least partially explain its poor response in vitro to antigenic stimulation. All three attributes could be connected to lack of pathogenicity of this line in vivo. These results support the contention that class II-restricted recognition of autoantigen within the neuroretina by uveitogenic T lymphocytes must occur as an initial step in the pathogenesis of EAU. A defect in this step will preclude pathogenesis regardless of some other functional attributes possessed by effector T cells, such as production of inflammatory lymphokines and expression of adhesion molecules.
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PMID:Uveitogenic T lymphocytes in the rat: pathogenicity vs. lymphokine production, adhesion molecules and surface antigen expression. 752 41

Recently, a complete bidirectional circuit between the immune and neuroendocrine systems has been documented. Previous reports from this laboratory have shown that there are complex reciprocal relationships between immune and hypothalamic-pituitary-adrenal (HPA)-axis function in major depression. To further examine the immune-endocrine relationships, this study investigates plasma baseline cortisol and prolactin secretion in relation to plasma interleukin-6 (IL-6) and soluble IL-2 receptor (sIL-2R) levels in 34 healthy controls and 56 major depressed patients. There were significant positive correlations between IL-6 or sIL-2R and plasma cortisol in major depressed subjects and in the combined group of major depressed and healthy subjects. There were also significant positive correlations between plasma prolactin and sIL-2R concentrations in major depressed subjects and in the combined groups of normal and major depressed subjects.
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PMID:Immunoendocrine aspects of major depression. Relationships between plasma interleukin-6 and soluble interleukin-2 receptor, prolactin and cortisol. 766 25

A multiple immunodeficiency, involving antibody- and cell-mediated responses in 10 Chinese Shar-Pei (CSP) dogs is described. Abnormal levels of serum IgM and IgA in most cases, and IgG in fewer cases characterized the immunoglobulin deficiencies. Decreased in vitro proliferative responses of pokeweed mitogen (PWM)-stimulated peripheral blood mononuclear cells (PBMC) were found in nine cases. Clinical presentation involved several organ systems and was associated with recurrent infections and malignancy. Sera from affected dogs suppressed PWM-stimulated cell proliferation of affected and normal dogs, but not cultures stimulated with PWM followed by recombinant IL-2 (rIL-2). In vitro supplementation of PBMC cultures with immunomodulatory guanosine analogs (GA) resulted in increased de novo IgG and/or interleukin-6 (IL-6) synthesis. Cells from five immunodeficient dogs showed in vitro evidence of GA- or rIL-2-dependent enhanced immunological responses. Since rIL-2-mediated activation of the IL-2 receptor and GA-mediated immunomodulation are reported to act through protein kinase C (PKC)-independent pathways, it is concluded that the IL-2 receptor is functional in these dogs and that cell activation through alternative pathways may restore immune responses in affected CSP dogs.
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PMID:A primary immunodeficiency syndrome in Shar-Pei dogs. 785 14

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

Rejection continues to be a major cause of graft loss in small intestine transplantation (SIT). We have studied, by semiquantitative reverse transcriptase PCR (rtPCR), the intragraft expression of cytokines relevant to rejection in a rat model. Heterotopic SIT grafts were performed from Lewis x Brown Norway F1 donors into Lewis recipients. The isograft control was Lewis into Lewis. Five animals in each isograft and allograft group were sacrificed on POD 3, 5, 7, 8, 9, 10, 12, and 14. mRNA was isolated from portions of the terminal ileum and rtPCR performed to amplify message for interleukin-2 (IL-2), IL-2 receptor (IL-2R), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma). Semiquantitative analysis was performed using 32P radionuclide incorporation and scintillation counting. The results were expressed as percent activity compared with beta-actin. Histologic correlation with cytokine expression was made. On POD 3 after SIT there was no evidence of rejection by histology and all cytokines studied showed no difference between the isograft and the allograft. On POD 5 the first evidence of mild rejection was seen on histology and IL-6, IFN-gamma, TNF-alpha showed a significant up regulation in the allograft that persisted through POD 14. mRNA for IL-2 was not significantly upregulated until POD 7 and persisted until POD 14. IL-2R was constitutively expressed in both isograft and allograft and was not a reliable predictor of rejection. Histologic rejection was moderately severe by POD 7 and severe between POD 8 and 14 correlating with the increasing expression of IL-6, IFN-gamma, and TNF-alpha. In summary, we have shown that increasing expression of mRNA for IL-6, IFN-gamma, and TNF-alpha not only correlated with severity of rejection but that upregulation began early when histologic evidence of rejection first occurred.
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PMID:The correlation of intragraft cytokine expression with rejection in rat small intestine transplantation. 794 Jun 88

We have recently shown that a single transfusion of red blood cells to normal human volunteers significantly increases the secretion of a variety of cytokines. In the present study we explored the in vitro effect of whole red blood cells on various T cell and monocytes functions of autologous human or mouse origin. This in vitro model would allow us to further determine in future studies the membranal determinants or the intracellular products of the RBC responsible for the enhancing effect. We demonstrate in this study that addition of autologous erythrocytes to human mononuclear cells or mouse spleen cell cultures results in enhancement of cellular responses to suboptimal concentrations of mitogens. These include cell proliferation, the secretion of IL-2, colony stimulating factor (CSF), interferon-gamma, tumor necrosis factor, and interleukin-6 by human MNC, and cell proliferation, IL-2, IL-3, and CSF by mouse spleen cells. The enhancing effect was dose dependent. Moreover, RBC are shown to directly enhance the expression of IL-2 receptors on both human and mouse cells without the need for the presence of mitogenic stimulation. The expression of IL-2R was measured both by acquisition of responsiveness to exogenous recombinant IL-2 and by immunofluorescence staining. We suggest that whole red blood cells exert a general enhancing effect on the secretion of a variety of cytokines and induce IL-2 receptor expression, probably through nonspecific interaction between membranal domains on erythrocytes and CD2 antigen on T cells.
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PMID:Enhancing effects of autologous erythrocytes on human or mouse cytokine secretion and IL-2R expression. 809 64

We have previously reported that transforming growth factor-beta 1 (TGF-beta 1) inhibits interleukin-6 (IL-6) induction by IL-2 and IL-1 in fresh human monocytes. We investigated the effects of TGF-beta 1 on the expression of tumoricidal activity induced by IL-2 or interferon-gamma (IFN-gamma) in human monocytes. We showed that TGF-beta 1 specifically inhibited, in a dose-dependent manner, IL-2-induced but not IFN-gamma-induced monocyte tumoricidal activity. The inhibitory effects of TGF-beta 1 on IL-2-activated monocytes were not caused by down-modulation of the IL-2 receptor beta (IL-2R beta) because the treatment of monocytes with IL-2 and TGF-beta 1 increased IL-2R beta mRNA expression. However, we found that TGF-beta 1 down-modulated IL-2-induced IL-2R gamma mRNA, which may be responsible for the TGF-beta 1 inhibition of monocyte activation by IL-2. The resistance of the IFN-gamma-induced activation to the inhibitory effects of TGF-beta 1 could be caused by the ability of IFN-gamma to decrease TGF-beta 1 receptor expression, as shown by cross-linking experiments. Overall, these results showed that TGF-beta 1 is a powerful inhibitor of IL-2- but not of IFN-gamma-induced activation of monocytes to a cytotoxic stage. This differential effect may be attributed to modulation of cytokine receptor expression.
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PMID:Inhibitory cytokine circuits involving transforming growth factor-beta, interferon-gamma, and interleukin-2 in human monocyte activation. 819 69

Human peripheral blood mononuclear cells (PBMCs) were cultured in vitro with various stimuli and in the presence or absence of a 5-lipoxygenase (5-LO) inhibitor, A-63162, to measure its effects on PBMC proliferation, interleukin-2 receptor (IL-2R) expression, interleukin-2 (IL-2) synthesis, interleukin-6 (IL-6) synthesis, and accumulation of messenger RNA for IL-2 or IL-6. A-63162 inhibited PBMC proliferation stimulated by phytohemagglutinin (PHA) and phorbol myristate acetate (PMA) plus A23187, IL-2 receptor expression stimulated by PHA, and IL-2 or IL-6 synthesis induced by PHA plus PMA or PMA plus A23187. At the same concentration, A-63162 inhibited accumulation of mRNA for IL-2 or IL-6 and also inhibited leukotriene B4 (LTB4) synthesis. Our data indicate that the 5-LO inhibitor A-63162 has immunosuppressive activity that may be due to inhibition of LTB4 production or to direct inhibitory actions of A-63162 on IL-2 and IL-6 synthesis.
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PMID:Inhibition of human mononuclear cell proliferation, interleukin synthesis, mRNA for IL-2, IL-6, and leukotriene B4 synthesis by a lipoxygenase inhibitor. 840 48

Many immunologic aspects of atopic dermatitis have been studied, but basic pathobiologic mechanisms of this disease remain unknown. In this study, we measured the production of interleukin-6 (IL-6) by peripheral blood T cells and monocytes from patients with atopic dermatitis in comparison to normal control subjects and patients with chronic psoriasis. We found that peripheral blood T cells isolated from patients with atopic dermatitis produced significantly higher levels of IL-6 (36.1 +/- 5.1 units/ml, n = 22) than T cells derived from either normal subjects (12.6 +/- 1.9 units/ml, n = 22) or patients with chronic psoriasis (26.7 +/- 4.1 units/ml, n = 7). T-cell activation was also measured in the patients with atopic dermatitis by soluble serum IL-2 receptor levels and were found to be significantly higher (623.7 +/- 8.1 units/ml, n = 8) than normal subjects (357.2 +/- 26.0 units/ml, n = 8). In contrast to the increased production of IL-6 by T cells in atopic dermatitis, there was no significant difference in the IL-6 production by peripheral blood monocytes derived from patients with atopic dermatitis compared to normal subjects. Thus, peripheral blood T cells derived from patients with AD spontaneously produce increased amounts of IL-6 compared to T cells from normal subjects, which may reflect the increased activation state of T cells in atopic dermatitis. These data support the concept that activated T cells or subsets of T cells may be important effector cells in mediating inflammatory activity in atopic disease.
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PMID:Increased interleukin 6 production by T cells derived from patients with atopic dermatitis. 844 Sep 9

In this study, we measured serially the serum levels of cytokines including interleukin-6 (IL-6), IL-8, soluble IL-2 receptor (sIL-2R) and tumour necrosis factor alpha (TNF-alpha) in 60 patients with Kawasaki disease (KD) and evaluated the clinical significance of these cytokines in predicting coronary aneurysm formation. Of the 60 patients, 12 were complicated with coronary aneurysm. Blood samples were collected within the 1st week after onset of fever, then once a week for the 1st month, and once a month for another 5 months. The serum levels of IL-6, IL-8, sIL-2R and TNF alpha were measured using an ELISA or RIA method. Our results show that the changes in serum IL-6 and IL-8 were faster than those of sIL-2R and TNF alpha. Within the 1st week, the serum levels of IL-6 and IL-8 were significantly higher in the patients with than in those without coronary aneurysm (P < 0.001). In addition, the serum levels of IL-6 and IL-8 obtained in the 1st week were highly correlated (P < 0.001) with those of C-reactive protein and erythrocyte sedimentation rate, and the serum levels of sIL-2R and TNF alpha were also increased at the 1st week reaching the highest level in the 2nd week. In the 2nd week, the serum levels of sIL-2R and TNF alpha were significantly higher in the patients with than in those without coronary aneurysm (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokines predict coronary aneurysm formation in Kawasaki disease patients. 848 78


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