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)

Interleukin-2 (IL-2)-like immunoreactivity and IL-2 receptor immunoreactivity have been reported in different brain regions, under normal and pathophysiological conditions. IL-2 stimulates hypothalamic corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) release and that of pituitary adrenocorticotropin. The amygdala, known to contain high levels of CRF, is involved in stress-related reactions, including regulation of the hypothalamo-pituitary-adrenal axis. IL-2 will release AVP from both the hypothalamus and the amygdala, which further supports a role for cytokine effects in the amygdala in neuroimmune interactions. In the present study, we compared the effects of IL-2, acetylcholine and norepinephrine on the in vitro release of CRF from the amygdala or hypothalamus. In addition, we used these release systems to evaluate the possible involvement of nitric oxide (NO)-mediated signaling in CRF release. IL-2 stimulates CRF release in both regions, in a calcium- and dose-dependent manner. Nitroprusside, an NO generator, also induces CRF release. This IL-2-induced CRF release is antagonized by Ng-methyl-L-arginine and hemoglobin, known NO antagonists. Finally, norepinephrine and acetylcholine induce CRF release. The norepinephrine-induced CRF release is antagonized by phentolamine and propanolol and the acetylcholine-induced release by atropine and mecamylamine, which suggests the involvement of both alpha and beta adrenergic receptors and both muscarinic and nicotinic receptors. The acetylcholine-induced CRF release is antagonized by Ng-methyl-L-arginine, but the norepinephrine-induced response is not. These data support the suggestion that the amygdala may participate in communications between the neuroendocrine and immune systems.
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PMID:Interleukin-2 (IL-2) induces corticotropin-releasing factor (CRF) release from the amygdala and involves a nitric oxide-mediated signaling; comparison with the hypothalamic response. 785 99

Interleukin-2 (IL-2) signaling requires the dimerization of the IL-2 receptor beta.(IL-2R beta) and common gamma (gamma c) chains. Mutations of gamma c can result in X-linked severe combined immunodeficiency (XSCID). IL-2, IL-4, IL-7 (whose receptors are known to contain gamma c), and IL-9 (whose receptor is shown here to contain gamma c) induced the tyrosine phosphorylation and activation of the Janus family tyrosine kinases Jak1 and Jak3. Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively; IL-2 induced Jak3-IL-2R beta and increased Jak3-gamma c associations. Truncations of gamma c, and a gamma c, point mutation causing moderate X-linked combined immunodeficiency (XCID), decreased gamma c-Jak3 association. Thus, gamma c mutations in at least some XSCID and XCID patients prevent normal Jak3 activation, suggesting that mutations of Jak3 may result in an XSCID-like phenotype.
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PMID:Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID. 797 58

The authors have recently shown the feasibility of eradicating brain tumors using in vivo retroviral-mediated transduction of tumors with the herpes simplex thymidine kinase (HStk) gene and ganciclovir therapy. However, thymidine kinase-transduced subcutaneous tumors in immunocompromised (athymic) mice were less responsive to this therapy than in immunocompetent animals, suggesting a role of the immune system in the process of tumor eradication. Broad suppression of humoral and cell-mediated immunity is found in patients with malignant gliomas. Interleukin-2 (IL-2) production and IL-2 receptor expression are decreased in gliomas patients. These findings and the proposed association between lymphocytic infiltration of brain tumors and survival suggest that immune response modifiers may be useful in treating glioma patients. To evaluate the role of local cytokine expression by tumor cells, alone or combined with HStk gene transfer and ganciclovir therapy, the authors investigated the efficacy of tumor (9L gliosarcoma) eradication in Fischer rats by in vitro and in vivo tumor transduction with the IL-2 gene alone or with a combined vector carrying both the HStk and IL-2 genes. Tumors injected with HStk vector-producer cells alone, with or without ganciclovir, and rats inoculated in the brain and subcutaneously with 9L cells that had previously been transduced in vitro served as controls. Murine vector-producer cells (3 x 10(6)/50 microliters) were injected into the brain tumors 7 days after tumor inoculation. Ganciclovir (15 mg/kg) was administered intraperitoneally twice daily for 10 days to animals that received HStk with or without IL-2 vector-producer cells, starting 5 days after producer-cell injection. The experiment was repeated with continuous daily treatment of all rats with oral dexamethasone (0.5 mg/kg). Rats were sacrificed 21 days after tumor inoculation, and the brains were removed for histological and immunohistochemical analysis for IL-2. Within each experimental group, tumors were found in a similar proportion in the dexamethasone-treated and untreated rats. Large brain tumors developed in all 10 rats that had been inoculated with 9L cells which had been pretransduced in vitro with the IL-2 gene, whereas only three of eight rats receiving subcutaneous inoculation of similar cells developed palpable tumors. No enhancement of tumor eradication was observed by adding the IL-2 gene in the HStk vector construct compared to the use of the vector with HStk alone. Lymphocytic infiltration was absent in all dexamethasone-treated rats but was observed in all treatment groups not receiving steroids.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:In vivo transfer of the human interleukin-2 gene: negative tumoricidal results in experimental brain tumors. 811 67

Adoptive immunotherapy is used to treat malignant tumors resistant to conventional therapeutic modalities. Patients with metastatic melanoma, renal cell carcinoma or mesothelioma are most likely to benefit from this treatment. Tumor infiltrating lymphocytes (TIL) contain tumor specific killer cells and are found to be the most effective. When TIL is not available or until it can be produced in sufficient amount, autologous activated lymphocytes (AAL) are an alternative. AAL are leukapheresed lymphocytes, activated by conditioned medium from OKT3 stimulated autologous lymphocytes. Subcutaneous IL-2 and oral cimetidine are also administered to support the reinfused AAL and to inhibit activation of CD8+ suppressor cells, respectively. To improve the yield and activation of reinfused lymphocytes, addition of IL-2 to the culture medium was tested in different time intervals after the onset of the culture. Interleukin-2 added in the first or second day i) improved the yield of activated lymphocytes; ii) increased the expression of activation markers CD25 (IL-2 receptor) and HLA-DR and iii) augmented killing of tumor cells. Later addition of IL-2 had no or negative effects. In vitro priming of peripheral blood mononuclear cells with autologous or allogeneic but histologically identical tumors was used to increase tumor-specificity of AAL. Autologous serum, containing antibodies specific to tumor cells, facilitated antigen presentation and yielded cytotoxic lymphocytes capable of efficiently killing tumor cells.
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PMID:Adoptive immunotherapy with activated peripheral blood lymphocytes. 815 78

Interleukin-2, a polypeptide lymphokine that induces proliferation of antigen- or mitogen-stimulated T cells, was first described as "T-cell growth factor" by Morgan et al. in 1976. IL-2 is one of several lymphocyte-produced messenger regulatory molecules that modulate immunocyte function. The main secretory source of IL-2 is the T-helper cell. In 1983, Taniguchi and colleagues isolated a human IL-2 complementary DNA clone from a high-producer Jurkat leukemic cell line, and established its nucleotide sequence. In 1984, Rosenberg et al. described the isolation of cDNA clones of the gene for IL-2 from the Jurkat cell line, its expression in Escherichia coli and its biological characteristics. The mature secreted protein contains 133 amino acids, constituting a calculated molecular weight of 15,420. Since the discovery of IL-2 and its T-cell growth-promoting activity, extensive research has revealed the complex nature of its immunologic effects, both in vitro and in vivo. The immunopotentiating activities, encouraging in vitro results, plus successful therapy of animal tumors in preclinical studies provided the rationale for investigation of IL-2 in patients with advanced malignancy and immunodeficiencies. The IL-2 receptor has been found to have an unexpected by unusual structure in that it is composed of two separate chains designated alpha (p75) and beta (p55). Recently, it has been discovered the 3rd gamma-chain by Sugamura et al. Clinical trials of IL-2 in patients with cancer have been done by many researchers. The clinical trials has reviewed briefly.
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PMID:[Interleukin-2 (IL-2)]. 815

Interleukin-2 (IL-2) was administered locally by constant intra-arterial infusion in four escalating doses from 3 x 10(4)-3 x 10(7) IU/day to 12 patients with squamous cell carcinoma of the head and neck (SCCHN) in a phase I trial. Lymphocyte phenotypic markers and serum cytokine concentrations were measured over the course of treatment. Serum IL-1-alpha, -beta and IL-6 were not induced at any dose level. Tumour necrosis factor (TNF)-alpha was induced in the 2 patients who showed a clinical response (at the lowest dose) as well as in 4/10 of the non-responders. In addition TNF-beta was induced in 3/10 and IFN-gamma in 5/10 non-responders. Soluble IL-2 receptor concentrations were increased at the two higher doses. The highest dose of IL-2 produced a lymphocytosis after day 5 until the end of administration reflected by a general rise in lymphocyte phenotypic markers. CD25, CD3/HLA-DR and CD56 showed an additional upregulation not accounted for by the lymphocytosis with a suggestion of a bell-shaped dose-response curve for CD25 and CD3/HLA-DR. Administration of IL-2 in this manner has been shown to be well tolerated and has some anti-tumour activity at low doses, with little toxicity.
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PMID:Immune changes in peripheral blood resulting from locally directed interleukin-2 therapy in squamous cell carcinoma of the head and neck. 818 May 73

Interleukin-2 (IL-2) is a 133 amino acid alpha-helical protein secreted by activated T-cells. Combinatorial cassette mutagenesis was used to investigate the functional role of a continuous five amino acid region of IL-2 suspected to interact with the intermediate-affinity IL-2 receptor. A limited random library of IL-2 mutants was constructed in which residues 17-21 (Leu-Leu-Leu-Asp-Leu) were simultaneously mutated. The proteins were produced in an Escherichia coli expression system and screened in a biological assay for their ability to mediate the proliferation of a murine IL-2-dependent cell line. From the over 2600 clones examined, only 42 exhibited significant activity, confirming the functional importance of this region. Selected clones were purified and further characterized by biological and receptor binding assays. Viewed in the context of the recently revised 2.5-A crystal structure for IL-2, these results suggest the following conclusions: both Asp20 and Leu21, as shown by their sensitivity to mutation, are the functionally more important residues in this region, but for different reasons. Asp20 is solvent-accessible and likely plays a direct receptor contact role as previous studies have indicated. Leu21, in contrast, is completely buried in the hydrophobic core of the protein. Substitutions at this position, even a conservative Leu-->Val substitution, were found to perturb the precise hydrophobic packing arrangements that are critical for activity, resulting in a significant loss of function. In addition, one of the analogs identified in the screen was found to be 2-3 times more potent than the wild-type protein.
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PMID:Mutagenic analysis of a receptor contact site on interleukin-2: preparation of an IL-2 analog with increased potency. 820 93

It was previously found that the cell-mediated immune response involved in protection against Treponema pallidum is distinctly suppressed during some periods in the course of syphilis infection in rabbits. This may be a result of the weak ability of cells to produce Interleukin-2 (IL-2) as well as of IL-2 absorption. The ability of peripheral blood mononuclear cells (PBMC) of syphilitic rabbits to produce IL-2 develops within the first two weeks after infection reaching a maximum in about the eleventh week. In infection of longer duration, this capability was distinctly lowered. This low level of activity (no higher than in PBMC of normal rabbits) was maintained for 31 weeks. The ability of PBMC to absorb IL-2, in parallel with its production, was found at the same time in the course of syphilis infection (7-11 weeks). In long-lasting syphilis (more than 12 weeks) both abilities seem to be inhibited. Sera of syphilitic rabbits were found to have a higher level of IL-2 inhibitor than those of normal rabbits. Only in syphilis lasting 9 to 11 weeks, when the production of IL-2 was the greatest, was the level of IL-2 inhibitor nearly the same as in normal rabbit sera. In syphilis lasting longer, the increased level of inhibitor was accompanied by a decreased ability of cells to produce IL-2. These findings suggest that IL-2 inhibitor may be bound to IL-2 or IL-2 receptor on T lymphocytes and in this way would lead to weakening of T cell function and resistance against Treponema pallidum infection.
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PMID:The ability of peripheral blood mononuclear cells of rabbits infected with Treponema pallidum to produce IL-2. 827 56

Interleukin-2 is a lymphocytotrophic hormone that plays a critical role in the host's normal immune response. Deficiencies in the production of IL-2 are likely to be important in the pathogenesis of certain infectious and malignant diseases. A better understanding of IL-2 and its potential applications in the treatment of human disease will come about with continued efforts in at least two areas. First, we must continue to characterize IL-2 receptor expression on the cells that normally use IL-2, in an attempt to fully elucidate their functional responsiveness to this hormone in vitro and their physiologic role in vivo. Second, we should proceed with clinical trials that use rIL-2 in an effort to assess cellular and humoral responses in vivo, and to learn more about the ability of rIL-2 to provide additional defense against persistent infection or malignancy in both immunocompromised and cancer patients.
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PMID:Low-dose recombinant interleukin-2 therapy: rationale and potential clinical applications. 828 89

Interleukin-2 (IL-2) level was measured in sera and in supernatants of Purified Protein Derivatives of Tuberculin (PPD) stimulated peripheral blood mononuclear cells (PBMC) cultures from children with active primary pulmonary tuberculosis (TB), or adenitis caused by mycobacteria of the group Mycobacterium avium, intracellulare, scrofulaceum (MAIS). The control groups included BCG vaccinated children (BCG) and children with negative skin test to PPD (NST). High mean IL-2 level was exclusively found in sera of mild TB patients (MTB), and not in sera of MAIS infected or BCG vaccinated children. The IL-2 level increased even more in MTB during treatment. In severe TB (STB) the IL-2 level was not elevated before treatment, but increased also during treatment. IL-2 production in supernatants of PPD stimulated PBMC cultures was increased in MTB as well as in MAIS and BCG subjects. Further, soluble IL-2 receptor (sIL-2R) levels were measured in the different groups of children. With the exception of the STB group, there was otherwise no significant increase of the receptor in the sera levels between groups. During treatment the sIL-2R levels decreased in MTB as well as in STB. A slight but non significant augmentation was found in the supernatants of PBMC cultures stimulated with PPD. This work suggests, along with other referable studies, that IL-2 and sIL-2R levels are inversely modulated by the disease. Indeed, the IL-2 seems to increase in MTB comparatively to NST children, and in treated TB comparatively to non treated TB children. On the other hand, the sIL-2R level was found to decrease in TB under treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-2 and soluble interleukin-2 receptor levels in children with active pulmonary tuberculosis and atypical mycobacterial adenitis. 849 Jan 4


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