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)

A pattern of aberrations in the T-cell cytokine system that is typical for autoimmune disorders has also been reported in patients with schizophrenia, namely a decreased interleukin-2 (IL-2) production and increased levels of the soluble IL-2 receptor (sIL-2R). It has also been reported that the production of interferon-gamma (IFN-gamma) may be lowered. In a longitudinal design, we studied the production of both IFN-gamma and IL-2 and their correlation in patients with schizophrenia during treatment and investigated whether associations exist between cytokine production and clinical variables. The production of IFN-gamma and IL-2 was measured in equal numbers (n = 29) of patients with schizophrenia (DSM-IV) and controls who were matched for age and gender. Patients were measured 1 day after admission (T1), after 14 (T2) and 28 (T2) days of treatment. Psychopathology was assessed after these times. The production of both IFN-gamma and IL-2 was significantly lower in patients than in controls throughout the whole investigation period (T1-T3). The productions of both cytokines were significantly correlated in controls (r = 0.60, P </= 0.001) as well as in patients with schizophrenia (mean production T1-T3: r = 0.71, P </= 0.001). No associations between cytokine measurements and psychopathology or age-at-onset could be found. Our findings of lowered and correlated IFN-gamma and IL-2 production indicate that alterations in the cytokine system of patients with schizophrenia might resemble those in autoimmune disorders. It is suggested that these immunological abnormalities are associated with acute exacerbation, rather than with a clinical subtype of schizophrenia.
 ...
PMID:Decreased in vitro production of interferon-gamma and interleukin-2 in whole blood of patients with schizophrenia during treatment. 1082 42

We investigated the in vitro effects of combining interleukin-18 (IL-18) and IL-2 on human lymphocytes. The combined use of these two cytokines synergistically enhanced the proliferation, cytolytic activity, and interferon-gamma production of peripheral blood mononuclear cells. Phenotypic analysis revealed a preferential expansion of CD56+CD3- cells and an up-regulation of IL-2 receptor-alpha expression on natural killer cells. Isolated natural killer cells showed a substantial increase in proliferation and cytotoxicity compared with CD4+ and CD8+ T cells. The combined use of IL-18 and IL-2 should be considered a viable strategy to induce an antitumor response in vivo.
 ...
PMID:Interleukin-18 (IL-18) synergizes with IL-2 to enhance cytotoxicity, interferon-gamma production, and expansion of natural killer cells. 1122 75

UV radiation was recently found to hinder interferon-gamma from exerting its biological effects by inhibiting the phosphorylation of signal transducer and activator of transcription (STAT)-1, a crucial signal transducing protein in the interferon-gamma pathway. Because this activity by UV may contribute to its immunosuppressive properties we studied whether this is specific for STAT1 or whether UV also affects other members of the STAT family. STAT5 is crucially involved in signaling of interleukin (IL)-2, enabling up-regulation of the IL-2 receptor alpha chain, an essential component of the high affinity IL-2 receptor. Exposure of the murine T cell line CTLL to IL-2 caused tyrosine phosphorylation of STAT5 that was remarkably reduced when cells were exposed to UV. Accordingly, STAT5 binding activity was significantly impaired in UV-exposed cells. In contrast, IL-2-induced tyrosine phosphorylation of the kinases Jak1 and Jak3 located upstream of STAT5 was not affected by UV. The effect of UV on STAT5 phosphorylation was antagonized by orthovanadate, implying involvement of a phosphatase in this process. Accordingly, up-regulation of the IL-2 receptor alpha chain was reduced in cells that were treated with IL-2 plus UV. Because STAT5-mediated IL-2 effects are vital for normal immune functions, inhibition of STAT5 signaling by UV may contribute to its well known immunosuppressive properties.
 ...
PMID:Ultraviolet radiation inhibits interleukin-2-induced tyrosine phosphorylation and the activation of STAT5 in T lymphocytes. 1127 1

Human immunodeficiency virus (HIV), the retrovirus associated with acquired immune deficiency syndrome (AIDS), induces a spectrum of immune abnormalities including a state of anergy in the host. This state is due to the binding of HIV envelope glycoprotein moieties to CD4 molecules and chemokine receptors. Resulting decrease in antigen presenting cell function and the interference with functioning of positive and negative regulatory molecules involved in signal transduction have an anergizing effect on the immune system. This effect is exemplified by diminished production of interleukin-2 (IL-2) and interferon-gamma and reduced expression of IL-2 receptor by CD4 helper cells of HIV patients. These immune abnormalities lead to clinically relevant immunological phenomena such as Type-1 to Type-2 switch, decrease in delayed-type hypersensitivity dermal reaction, etc. Insight into these interesting phenomena could pave the path for favorably altering the immunological milieu for drug and vaccine trials.
 ...
PMID:Anergy and human immunodeficiency virus infection. 1135 64

Natural killer (NK) cells play important roles in innate immunity by lysing tumor and virally infected cells and by producing cytokines including interferon-gamma. While NK cell progenitors have been described in the fetal thymus, NK cell generation from hematopoietic stem cells (HSC) in the bone marrow (BM) occurs throughout life, and in athymic mice and humans. Interleukin (IL)-15 promotes NK development in vitro and is essential for the generation of normal numbers of NK cells in vivo. By characterizing BM cells expressing IL-15 receptor components, we found marked heterogeneity within the IL-2 receptor beta chain(+) (CD122(+)) subset, which included cells uniquely committed to the NK lineage. These CD122(+) NK cell precursors (NKP) are negative for markers used to identify mature NK cells, including NK1.1, DX5 and members of Ly-49 family, and fail to demonstrate natural cytotoxicity against susceptible target cells. In vitro culture of NKP generates mature lytic NK1.1(+) cells at high frequencies, while they do not give rise to T, B, myeloid or erythroid cells under appropriate conditions. NKP lack transcripts associated with early B and T cell differentiation (pTalpha, lambda5 and CD3epsilon), but express a group of genes (IL-15Ralpha, Id2, GATA-3 and Ets-1) and the 2B4 marker, which may define NK cell commitment. We propose that NKP represent the earliest adult BM precursor uniquely restricted to the NK cell lineage.
 ...
PMID:Identification of committed NK cell progenitors in adult murine bone marrow. 1143 87

The plasma levels of a panel of cytokines and cytokine-associated molecules (IL-1alpha, IL-2, IL-4, IL-6, IL-10, IL-12, IL-15, macrophage colony-stimulating factor (M-CSF), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), soluble IL-2 receptor (sIL-2R), soluble tumor necrosis factor receptor I or II (sTNFRI or II)) were assessed in 56 plasma samples of 13 pediatric patients undergoing hematopoietic stem cell transplantation (HSCT, bone marrow in 12 and cord blood in one) from unrelated donors. Eight patients developed severe (grade III-IV) acute GVHD (aGVHD). The plasma IL-6, IL-10, M-CSF, sTNFRI and II levels were significantly high in the severe aGVHD group compared to the mild aGVHD group (grade 0-II). The plasma IL-15 level increased transiently in the early period following HSCT and remained high in the severe aGVHD group even after 4 weeks following HSCT. Based on analysis of the correlations between the kinetics of the plasma cytokine levels after HSCT and the clinical manifestations of aGVHD, IL-15 and/or M-CSF were involved in the development of aGVHD, following elevation of the plasma IL-10 and sTNFRI or II levels. These kinetics suggest that IL-10 and sTNFRs worked as suppressor cytokines and seemed to suppress clinical manifestations of aGVHD. Furthermore, it seemed that the plasma ratio of IL-10/sTNFRII from 5 to 12 weeks following HSCT was linked to the poor outcome in the patients with severe aGVHD, suggesting that IL-10 plays an important role in protecting hosts from transplantation-related complications, including GVHD.
 ...
PMID:Kinetics of plasma cytokines after hematopoietic stem cell transplantation from unrelated donors: the ratio of plasma IL-10/sTNFR level as a potential prognostic marker in severe acute graft-versus-host disease. 1155 Oct 26

Interleukin-10 (IL-10) is a multifunctional cytokine that can exert suppressive and stimulatory effects on T cells. It was investigated whether IL-10 could serve as an immunostimulant for specific CD8(+) cytotoxic T cell (CTL) in vivo after vaccination and, if so, under what conditions. In tumor prevention models, administration of IL-10 before, or soon after, peptide-pulsed primary dendritic cell immunization resulted in immune suppression and enhanced tumor progression. Injection of IL-10, however, just after a booster vaccine significantly enhanced antitumor immunity and vaccine efficacy. Analysis of spleen cells derived from these latter animals 3 weeks after IL-10 treatment revealed that the number of CD8(+) CD44(hi) CD122(+) T cells had increased and that antigen-specific proliferation in vitro was enhanced. Although cytotoxicity assays did not support differences between the various treatment groups, 2 more sensitive assays measuring antigen-specific interferon-gamma production at the single-cell level demonstrated increases in the number of antigen-specific responder T cells in animals in the vaccine/IL-10 treatment group. Thus, IL-10 may maintain the number of antitumor CD8(+) T cells. In adoptive transfer studies, the ability of IL-10 to maintain CTL function could be enhanced by the depletion of CD4(+) T cells. This suggests that IL-10 mediates contrasting effects on both CD4(+) and CD8(+) T cells that result in either immune dampening or immune potentiation in situ, respectively. Appreciation of this dichotomy in IL-10 immunobiology may allow for the design of more effective cancer vaccines designed to activate and maintain specific CD8(+) T-cell effector function in situ.
 ...
PMID:Interleukin-10 promotes the maintenance of antitumor CD8(+) T-cell effector function in situ. 1156 1

Many studies illustrate that physical or psychologic stressors can alter human immune function, which might predispose one to an increased susceptibility to infections. In the present study, we monitored immune responsiveness in 16 first-year medical students (age 23.8 +/- 2.2 years) during the first examination session. Baseline blood samples were collected 30 days prior to the first examination session. Subsequently, subjects were randomly assigned to two groups, and blood samples were collected at 24 h (POST24h) or 48 h (POST48h) after an examination. The percentage of CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD3(+)CD45RO(+), CD3(+)CD45RA(+), CD3(-)CD16(+)56(+), CD19(+), and CD14(+) cells in whole blood was examined to determine changes in circulating immune cell populations. Activation of peripheral blood mononuclear cells (PBMC) with a mixture of phorbol myristate acetate (PMA) and ionomycin or lipopolysaccharide (LPS) for 4 h was used to assess the distribution of interleukin-2 (IL-2)-secreting or interferon-gamma (IFN-gamma)-secreting CD4(+) and CD8(+) cells, as well as IL-1alpha-secreting CD14(+) cells. Activation with a combination of phytohemagglutinin (PHA) and LPS was used to assess secretion of IL-2, IFN-gamma, IL-4, IL-10, soluble IL-2 receptor-alpha (sIL-2Ralpha), IL-1beta, and IL-1R antagonist (IL-1Ra) by PBMC in 48-h cell culture. A significantly higher level of total T cells was found at POST24h, and CD14(+) was elevated at both POST24h and POST48h. The percentage of CD4(+) and CD8(+) cells significantly declined at POST24 and POST48h. A significant elevation in the percentage of memory T cells was observed at POST48h, whereas the percentage of naive T cells was elevated at POST24h and POST48h. These changes were accompanied by a significant decline in percentage of natural killer (NK) cells 24 h after the examination. The percentage of IL-2-producing CD4(+) and CD8(+) cells was significantly lower at POST24h, and the percentage of CD8(+)IFN-gamma(+) cells significantly declined at POST48h. The percentage of CD14(+)IL-1alpha(+) significantly declined at both POST24 and POST48h. A significant decrease was observed in IL-2 secretion 24 h after the examinations, and the secretion of IL-4 and IL-1beta significantly declined at POST48h. No changes in IFN-gamma, IL-10, sIL-2Ralpha, and IL-1Ra secretion were observed. We conclude that the stress outcomes of academic examinations in first-year medical students can significantly alter immune cell distribution and in vitro production and secretion of specific cytokines.
 ...
PMID:Immune responsiveness following academic stress in first-year medical students. 1157 63

Activation of dendritic cells (DCs) and macrophages by infectious agents leads to secretion of interleukin 12 (IL-12), which subsequently induces interferon-gamma (IFN-gamma) production by multiple cell types that include DCs and macrophages. In turn, IFN-gamma acts on macrophages to augment IL-12 secretion and to produce nitric oxide (NO), which eradicates infected microbes. We show here that in cytokine common gamma subunit-deficient and/or IL-2 receptor beta-deficient mice, production of IL-12, IFN-gamma and NO by DCs and macrophages was severely impaired, as was up-regulation of major histocompatibility complex class II and CD40. Similar phenotypes were observed in DCs and macrophages from IL-15-deficient mice but not in those from IL-2-deficient mice. This shows that the IL-15-IL-15R interaction is critical in early activation of antigen-presenting cells and plays an important role in the innate immune system.
 ...
PMID:Critical role of IL-15-IL-15R for antigen-presenting cell functions in the innate immune response. 1170 64

Cytokines are known to play a major role in the pathogenesis of mycosis fungoides, a cutaneous malignant neoplasm of CD 4 T cells. In the present study, we investigated the effect of AS101, a tellurium-based compound with immunomodulating properties, on the pattern of lymphokine production by peripheral blood mononuclear cells (PBMCs) from patients with mycosis fungoides. PBMCs were isolated from 35 patients with mycosis fungoides stage IA and IB before initiation of treatment and from 20 healthy sex and age-matched controls. Unstimulated and phytohaemagglutinin-stimulated PBMCs were tested with and without the addition of AS101. The production of interferon-gamma, interleukin 2 (IL-2), IL-2 receptor (IL-2R), interleukin 5 (IL-5) and interleukin 10 (IL-10) was determined by enzyme-linked immunosorbent assays. The effects of AS-101 on mycosis fungoides PBMCs were compared to those of healthy donor PBMCs. Significantly higher levels of IL-2R, IL-5 and IL-10 and significantly lower levels of interferon-gamma were found in the patients compared to the controls. There was no significant difference between the groups in the production of IL-2. AS101 inhibited the production of IL-2R, IL-5 and IL-10 and induced a significant increase in IL-2 levels in the mycosis fungoides PBMCs. These findings may have important clinical implications for the possible therapeutic benefit of AS101 in mycosis fungoides.
 ...
PMID:Cytokine profile of patients with mycosis fungoides and the immunomodulatory effect of AS101. 1172 Jan 71


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