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)

We evaluated adoptive immunotherapy using LAK cells combined with systemic administration of interleukin-2 (IL-2) in 11 patients with metastatic renal cell carcinoma. The LAK cells were generated by incubation in serum-free medium (AIM-V) supplemented with IL-2 (1,000 U/ml) for 4 days and were generally administered twice weekly (4 times/cycle). Daily administration of IL-2 (50 x 10(5) U) was started 3 days prior to the first LAK infusion and continued throughout the cycle. Each course of therapy comprised 1-6 cycles, with the total dose of LAK cells and IL-2 varying from 3.3-52.6 x 10(9) cells and 140-900 x 10(5) U, respectively. Clinical response was evaluated in terms of metastasis to specific organs (lung only: eight cases, lung and brain: one, lung and lymph nodes: one, lung and bone and pleuropericardium: one). The outcome was complete response in one patient, partial response in one, no change in six and disease progression in three. The response rate was 18.8%. This therapy was most effective against pulmonary metastases. Adverse reactions to LAK cell infusion included fever, headache, and chills. Eosinophilia and weight gain due to IL-2 administration were also observed. However, all of these symptoms were transient and no serious side effects occurred. In these patients, the proportion of natural killer (NK) cells (CD16) and cells with IL-2 receptor (CD25) among PBL was increased markedly in the early phase of therapy, and activated T cell (CD3+DR+) and suppressor T cells (CD8+11+) increased significantly at a later phase. It was suggested that the clinical response would be expected in case of increasing of CD16 cells or CD25 cells and augmentation of NK or LAK activity. Our results indicate that this regimen of adoptive immunotherapy shows some promise for the treatment of advanced renal cell carcinoma.
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PMID:[Study of adoptive immunotherapy for metastatic renal cell carcinoma with lymphokine-activated killer (LAK) cells and interleukin-2. II. Clinical evaluation]. 832 Aug 88

Eosinophilic endomyocardial disease represents a major evolutive risk in chronic eosinophilia-associated disorders. Eosinophil granule proteins appear to be involved in cardiac injury, but the mechanisms leading to eosinophil infiltration and degranulation are not clear. Interleukin-5 (IL-5) has been recently shown to be produced by eosinophils and might play a role in both chemoattraction and degranulation of eosinophils. In four cases of eosinophilic diseases with severe cardiac failure, we evaluated the proportion of eosinophil phenotypes and the serum levels of eosinophil cationic protein (ECP) and soluble IL-2 receptor (sIL-2R), markers of disease activity in the hypereosinophilic syndromes. All four patients showed a markedly increased proportion of hypodense eosinophils with elevated serum ECP and sIL-2R levels. In all four patients, extracellular deposition of eosinophil granule proteins and features of eosinophil activation were observed in cardiac tissues. The synthesis of IL-5 by eosinophils was detected in myocardial sections and blood cells by in situ hybridization and by immunostaining with a monoclonal antibody against human IL-5. Sixty percent to 90% of tissue eosinophils expressed IL-5 mRNA and IL-5 protein. These data suggest that IL-5 can be produced by eosinophils at the sites of myocardial tissue damage and might participate in local eosinophil activation.
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PMID:Synthesis of interleukin-5 by activated eosinophils in patients with eosinophilic heart diseases. 836 5

The eosinophilia-myalgia syndrome (EMS) has been associated with ingestion of L-tryptophan (L-TRP) produced by a single manufacturer. Epidemiological data implicated 1,1'-ethylidenebis (L-tryptophan) (EBT) (peak 97 or peak E) as a possible etiologic agent. We showed previously that Lewis rats treated with the L-TRP implicated in EMS develop fasciitis and perimyositis similar to those seen in human EMS. We now report the pathology associated with the treatment of Lewis rats with synthetic EBT and/or L-TRP. All animals treated for 6 wk with case-associated L-TRP or EBT developed significant myofascial thickening, compared with animals in the vehicle control and control L-TRP groups. However, even those animals receiving the control L-TRP showed a mild but significant increase in the thickness of the myofascia, compared with vehicle-treated control animals. All animals except vehicle controls also exhibited significant pancreatic pathology, including fibrosis and acinar changes. Only animals treated with case-associated L-TRP for 6 wk showed evidence of immune activation with increased frequency of CD8, Ia, and IL-2 receptor-positive cells in the peripheral blood. Animals receiving L-TRP or EBT for < 6 wk did not show significant differences in myofascial thickness, although these animals did show pancreatic acinar changes. Although these results demonstrate for the first time the pathological effects of EBT, they do not rule out the possibility that other impurities in the EMS-case-associated L-TRP may also contribute to some of the features of EMS.
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PMID:Pathological and immunological effects of ingesting L-tryptophan and 1,1'-ethylidenebis (L-tryptophan) in Lewis rats. 845 62

A 43-year-old male with newly diagnosed hairy cell leukaemia underwent a single course of 2-chlorodeoxyadenosine (2-CdA). Skin rash, facial swelling and marked eosinophilia developed 20 d after treatment and were resolved by 7 d of steroid therapy. Eosinophil peak in peripheral of the eosinophil population showed a high expression of the IL-2 receptor alpha-chain (CD25), representing up to 94% of gated cells. HLA-DR and CD4 antigens were constantly negative; eosinophils strongly reacted with the secretory form of the eosinophil cationic protein (ECP), recognized by EG2 monoclonal antibody. IL-5 serum levels were markedly elevated at the onset of eosinophilia, returned to normal levels after its disappearance and positively correlated with eosinophil count (r = 0.94, P = 0.016). Eosinophilia is an uncommon finding after treatment with 2-CdA. It is unclear whether these phenomena represented a true allergic reaction to the drug or the effect of massive tumour cell lysis and haemopoietic pancytopenia with immunosuppression, which induced the release of IL-5 and possibly other cytokines.
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PMID:Hypereosinophilia during 2-chlorodeoxyadenosine treatment for hairy cell leukaemia. 860 11

Interleukin-2 (IL-2) is an essential growth factor for T cells. Previous studies have shown that human peripheral eosinophils respond to IL-2 in chemotaxis and express the IL-2 receptor (CD25). In addition, eosinophils have been shown to transcribe messenger RNA for IL-2. The aim of the present study was to determine whether eosinophils translate mRNA for IL-2 and to determine the site of intracellular localization. By immunocytochemistry, an average of 9% of cells showed cytoplasmic staining for IL-2 in freshly isolated unstimulated blood eosinophils obtained from asthmatic subjects who were not receiving oral corticosteroid treatment (n = 5). Freshly isolated, disrupted, highly purified eosinophils (> 99%, by CD16- immunomagnetic selection) contained an average of 6 pg/10(6) cells of IL-2 measured by a specific enzyme linked immunosorbent assay (ELISA) (n = 7). Purified eosinophil incubated with serum-coated Sephadex beads showed an increase in the amount of intracellularly-retained IL-2 (26.2 +/- 7.2 pg/10(6) cells) with some evidence for release of this cytokine but only in three out of six eosinophil preparations (range 1.3-5.8 pg/10(6) cells). The intracellular localization of IL-2 was determined by fractionation of the cells on a linear (0-45%) Nycodenz gradient in sucrose buffer followed by detection of IL-2 in the fractions using an IL-2-specific ELISA and dot blotting. The majority of the IL-2 detected co-eluted with known eosinophil granule markers (i.e. major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO) and beta-hexosaminidase) but small quantities were also detected in the cytosolic (lactate dehydrogenase-(LDH) associated) and membrane (CD9+) fractions. Immunogold labelling of intact eosinophils using an anti-IL-2 monoclonal antibody confirmed IL-2 immunoreactivity in association with the eosinophil crystalline granule cores. These data are consistent with the hypothesis that eosinophils synthesize, release and store IL-2 largely within cystalloid granules. This stored IL-2 may serve as a reservoir for rapid release of IL-2 in inflammatory reactions associated with eosinophilia.
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PMID:Identification of interleukin-2 in human peripheral blood eosinophils. 866 29

To explore the pathophysiology of patients with reactive eosinophilia from unknown cause, we measured the eosinophil colony stimulating factor (Eo-CSF) activity in the interleukin-2 (IL-2) stimulated lymphocyte conditioned medium (CM) prepared from 22 patients with reactive eosinophilia. Eo-CSF activity, the levels of interleukin-5 (IL-5) and granulocyte-macrophage colony stimulating factor (GM-CSF) were increased in the CM from patients with high IgE levels. Hydrocortisone decreased the level of Elo-CSF in the CM. Elevated serum levels of soluble IL-2 receptor (sIL-2R) were presented in 13 out of 15 patients with eosinophilia. The sIL-2R levels in patients with marked eosinophilia (>3000/mu l) were higher than those in patients with mild eosinophilia (< or = 3000/mu l). High sIL-2R levels were noted in T cell CM from 3 out of 15 patients and in eosinophil CM from 1 out of 4 patients. These data suggested that lymphocyte from eosinophilic patients with elevated IgE produce Eo-CSF, IL-5 and GM-CSF by IL-2 stimulation. Eo-CSF production is inhibited by hydrocortisone. SIL-2R is released from lymphocyte and in some case may be released from eosinophils.
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PMID:[Eosinophil colony stimulating factor (Eo-CSF) activity and soluble interleukin-2 receptor (sIL-2R) in patients with reactive eosinophilia]. 885 12

Glucocorticoids (GC) have long been used as the most effective agents for the treatment of allergic diseases accompanied by eosinophilia such as chronic asthma and atopic dermatitis. The development of chronic eosinophilic inflammation is dependent on interleukin-5 (IL-5), a selective eosinophil-activating factor, produced by helper T cells. To delineate the regulatory mechanisms of human IL-5 synthesis, we established allergen-specific CD4+ T-cell clones from asthmatic patients. GC efficiently suppressed IL-5 synthesis of T-cell clones activated via either T-cell receptor (TCR) or IL-2 receptor (IL-2R). Induction of IL-5 mRNA upon TCR and IL-2R stimulation was totally inhibited by dexamethasone. Human IL-5 promoter/enhancer-luciferase gene construct transfected to T-cell clones was transcribed on either TCR or IL-2R stimulation and was clearly downregulated by dexamethasone, indicating that the approximately 500-bp human IL-5 gene segment located 5' upstream of the coding region contains activation-inducible enhancer elements responsible for the regulation by GC. Electrophoretic mobility shift assay analysis suggested that AP-1 and NF-kappaB are among the possible targets of GC actions on TCR-stimulated T cells. NF-AT and NF-kappaB were not significantly induced by IL-2 stimulation. Our results showing that GC suppressed IL-5 production by human CD4+ T cells activated by two distinct stimuli, TCR and IL-2R stimulation, underscore the efficacy of GC in the treatment of allergic diseases via suppression of T-cell IL-5 synthesis.
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PMID:Two distinct pathways of interleukin-5 synthesis in allergen-specific human T-cell clones are suppressed by glucocorticoids. 910 9

We used a flow cytometry technique, the "FOG" method (formaldehyde and octylglucopyranoside), to investigate the expression of activation antigens, i.e., CD4, CD23, CD25, HLA-DR, and the EG2 epitope of eosinophilic cationic protein, on peripheral blood eosinophils (PBEs) in leukemic patients who had developed acute graft-vs.-host disease (aGVHD) with eosinophilia after allogeneic bone marrow transplantation (alloBMT) or leukocyte buffy coat infusion. A comparative analysis was performed in transplanted patients not affected by aGVHD and in other conditions commonly associated with peripheral eosinophilia, i.e., interleukin (IL)-2 immunotherapy and allergy. CD25, recognizing the p55 subunit of IL-2 receptor, was detected in all patients with aGVHD except two who, at the onset of eosinophilia, were already receiving methylprednisolone intravenously. The specificity of our findings is confirmed by the absence of reactivity with anti-CD25 mAb in PBEs from transplanted patients not affected by aGVHD. Interestingly, the expression of CD25 progressively declined after steroid therapy. CD25 was also expressed after rhIL-2 administration, probably reflecting analogous mechanisms of eosinophil activation. No aGVHD or rhIL-2-treated patient showed reactivity with anti-CD4, CD23, or HLA-DR. CD25 and CD23 antigens were detected in 29% and 36% of allergic patients only. The accessibility of the EG2 epitope was significantly enhanced in all study groups compared with controls. In vitro activation of normal eosinophils with phorbol 12-myristate 13-acetate upregulated CD9 and EG2 expression but failed to induce the CD25 antigen, suggesting that selective activating stimuli may be required. The functional significance of in vivo CD25 expression and the role of activated PBEs in the development of cellular and cytokine-mediated tissue destructive processes in aGVHD remain to be clarified.
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PMID:Immunophenotypic profile of peripheral blood eosinophils in acute graft-vs.-host disease. 947 6

To assess the eosinophil response to Plasmodium falciparum infection a cohort of initially parasite-free Ghanaian children was followed for 3 months. Seven of nine children who acquired an asymptomatic P. falciparum infection showed increase in eosinophil counts, while a decrease was found in seven of nine children with symptomatic malaria, and no change was observed in 14 children who remained parasite-free. In a hospital-based study, paediatric patients with cerebral malaria (CM), severe anaemia (SA), or uncomplicated malaria (UM) had uniformly low eosinophil counts during the acute illness followed by eosinophilia 30 days after cure. Plasma levels of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured as indicators of eosinophil activation. In spite of the low eosinophil counts, ECP levels were increased on day 0 and significantly higher in patients with CM (geometric mean (95% confidence interval) 8.5 ng/ml (6.8-10.7 ng/ml)) than in SA (4.7 ng/ml (3.0-7.5 ng/ml)) and UM patients (4.3 ng/ml (3.6-5.3 ng/ml), P < 0.001). A similar pattern was found for EPX. It thus appears that the low eosinophil counts may be due to tissue sequestration and destruction rather than decreased production. The plasma levels of the granule proteins correlated with levels of tumour necrosis factor and soluble IL-2 receptor, implicating inflammatory responses and T cell activation as causes of the eosinophil activation. By contrast, the eosinophil induction did not appear to be part of a Th2-like response. Eosinophil granule proteins may be important in both control of malaria infection and the pathogenesis of severe malaria.
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PMID:Increased eosinophil activity in acute Plasmodium falciparum infection--association with cerebral malaria. 964 95

Elevated IgE responses and eosinophilia observed in patients with atopic dermatitis (AD) may reflect increased responses of type 2 T-helper (Th2) cytokines with a concomitant decrease in interferon-gamma (IFN-gamma) production. However, the cross-regulation of Th1/Th2 derivation and function in AD patients are incompletely characterized. Therefore, we investigated serum levels of several cytokines [interleukin (IL)-18, IL-12, IL-10, IL-2 and IFN-gamma] in patients with AD to assess their possible relationships to the severity of disease. Serum IL-18 levels in AD patients were significantly higher than those in healthy controls [207 pg/mL; 95% confidence interval (CI), 172-242 pg/mL vs. 144 pg/mL; 95% CI, 116-178 pg/mL; P = 0.026]. Those IL-18 levels significantly correlated with eosinophil counts and serum soluble IL-2 receptor (sIL-2R) levels, and showed a tendency to correlate with clinical severity scores and serum IgE levels. IL-2 levels showed a significantly inverse correlation with serum IgE levels, and IL-12 levels clearly correlated with IL-10 levels. These results suggest the value of serum IL-18 levels as a parameter of AD activity and may support a possible role for IL-18 in the pathogenesis of AD. The inverse correlation between IgE levels and IL-2 levels suggests that IgE production may be inhibited by IL-2 in patients with AD. Furthermore, the correlation of IL-12 levels with IL-10 levels may support the previous reports that show the induction of IL-10 production by human natural killer cells and/or T cells stimulated with IL-12 in vitro.
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PMID:Serum cytokine levels in atopic dermatitis. 1207 14


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