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)

Both natural and adaptive immune responses were shown to be strikingly decreased in initial blood samples from 34 spinal cord injury and stroke patients. NK-cell function decreased to 24.8% (mean) 2 weeks after spinal cord injury in previously healthy young adults whose control group revealed a mean NK-cell function of 48.7%. This was accompanied at 2 weeks by increased plasma ACTH (mean of 17.0 pg/ml from 17 patients compared to a mean of 11.2 pg/ml from 12 controls) and urine free cortisol levels (mean of 152.1 micrograms/24 h from 9 patients compared to 53.6 micrograms/24 h from 15 controls). T-cell function and/or activation decreased to below normal values within 3 months after injury as revealed by lymphocyte transformation that was 32.8% of normal at 3 months. T-cell activation diminished as shown by a mean IL-2 receptor level of 179.3 units/ml in patients compared to 328.2 units/ml in controls. Serial monitoring of NK- and T-cell function revealed that specific physical rehabilitation therapy over a period of 6 months after injury restored NK- and T-cell function to near normal levels in most patients. This improvement was accompanied by a parallel rise in the patient's functional independence measurement scores. Results suggest critical neuroendocrine-immune system interactions in the restoration of immune function. Cortisol levels reverted to normal after 6 months of rehabilitation. Limited data suggest that natural immune system depression, NK-cell function, persists in spinal cord injury patients not receiving rehabilitation therapy (mean NK-cell lysis of 10.3%; p < 0.01).
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PMID:Neuroendocrine-immune interactions associated with loss and restoration of immune system function in spinal cord injury and stroke patients. 133 Dec 72

Pituitary cells were shown to release corticotropin (ACTH) in response to interleukin-2 (IL-2) and to express a protein that is related to the alpha-chain of the IL-2 receptor (IL-2R). The alpha-chain-like molecule was bound by a rat monoclonal antibody to the murine IL-2 receptor as well as to IL-2. Sodium dodecylsulfate-polyacrylamide gel electrophoretic analysis of the affinity-purified material from pituitary cells demonstrated a protein which was similar to that which was isolated from activated splenocytes. Thus, IL-2 and its receptor may be one of several hormone-receptor pairs utilized by both the immune and neuroendocrine systems for intersystem communication.
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PMID:Interleukin-2 induction of ACTH secretion: presence of an interleukin-2 receptor alpha-chain-like molecule on pituitary cells. 253 95

The neuropeptide arginine vasopressin (AVP) can replace the cytokine interleukin 2 (IL-2) as a T-cell mitogen for the induction of interferon gamma (IFN gamma) expression in splenic cultures. IL-2-like and IL-2 receptor immunoreactivity have been reported in different brain regions, under normal and pathophysiological conditions. Regulatory functions for IL-2 in the CNS have been suggested. In addition to the spleen, AVP might also mediate some IL-2 effects centrally. In the present study, we evaluated the effect of IL-2 on the in vitro release of AVP from the hypothalamus and amygdala. In addition, we used these release systems to study the possible involvement of NO-mediated signaling in AVP release, based on the reported detection of nitric oxide synthase (NOS) in the hypothalamus and amygdala. IL-2 rapidly stimulates AVP release in both regions, in a calcium- and dose-dependent manner. In addition, nitroprusside also induces AVP release. Norepinephrine also induces AVP release from both the hypothalamus, as well as the amygdala. The norepinephrine-induced AVP release is antagonized by phentolamine, but not by propranolol, suggesting an alpha-adrenergic receptor-mediated AVP response in both brain regions. The IL-2- and acetylcholine-induced AVP release is antagonized by Ng-methyl-L-arginine, indicating a role for NO in this AVP release. Ng-methyl-L-arginine does not affect the norepinephrine-induced AVP release. A stimulatory effect of IL-2 on hypothalamic CRF release and plasma ACTH has already been reported. Our results suggest that in addition to CRF, AVP may also mediate the IL-2 stimulation of ACTH secretion. These data further suggest that in addition to the hypothalamus, the amygdala may also play a role in the bidirectional communication between neuroendocrine and immune systems. Understanding the mode of interaction between IL-2 with AVP could clarify the pathophysiologic or toxic effects of high brain levels of IL-2.
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PMID:IL-2 induces vasopressin release from the hypothalamus and the amygdala: role of nitric oxide-mediated signaling. 752 33

The effects of long-term corticotropin-releasing hormone (CRH) infusion in the lateral ventricle of the rat on hypothalamic-pituitary-adrenocortical (HPA) axis parameters and on the immune system function were studied. Compared with infusion of vehicle, the CRH treatment produced a sustained overactivity of the HPA axis, as evidenced by elevated plasma ACTH and corticosterone levels, increased anterior pituitary POMC messenger RNA (mRNA) expression, and adrenal enlargement. Long-term CRH treatment also inhibited body weight gain and reduced thymus and spleen weight. In the CRH-treated animals, both Concanavalin A (Con A)-induced T lymphocyte proliferation and lipopolysaccharide (LPS)-induced B lymphocyte mitogenesis was largely suppressed. Surprisingly, interleukin-2 (IL-2) levels were higher in supernatants of splenocyte cultures from CRH-treated rats than in those of control animals. However, IL-2 receptor alpha chain (IL-2R alpha) mRNA expression after Con A stimulation was highly suppressed in the CRH-treated animals. In addition, Northern blot analysis of RNA from splenocytes isolated from spleens of CRH-treated rats revealed a marked expression of IL-1 beta mRNA, in contrast to the barely detectable levels of this cytokine in control animals. Moreover, incubation of total splenocytes and spleen macrophages with LPS resulted in an enhanced induction of IL-1 beta mRNA in cells of CRH-treated rats compared with that of control animals. When adrenalectomized rats were treated with CRH or vehicle, the effects of the CRH treatment on T and B cell proliferation, IL-2 production, and IL-1 beta mRNA expression were abolished. Thus, a continuously increased HPA axis drive results in disparate changes in immune system function. Whether the observed changes in cytokine expression should be regarded as physiologically adaptive adjustments in support of immune function or as potentially pathological anomalies remains to be elucidated.
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PMID:Long-term intracerebroventricular corticotropin-releasing hormone administration induces distinct changes in rat splenocyte activation and cytokine expression. 775 Apr 92

Interleukin-2 (IL-2) has been shown to stimulate ACTH secretion by anterior pituitary cells and has been implicated in pathophysiological processes of the pituitary and brain in several major neuropsychiatric disorders. The present study tested the hypothesis that IL-2 receptor-beta (IL-2R beta), a constitutively expressed and essential subunit for IL-2 signaling in lymphocytes, is expressed by AtT-20 pituitary cells and involved in transducing intracellular signals induced by IL-2. We isolated and sequenced three overlapping IL-2R beta cDNA clones from AtT-20 pituitary cells representing key regions of the gene protein coding sequence. These cDNA clones including conserved sequences shared by growth hormone and prolactin as well as intracytoplasmic Src and JAK family homology domains of nonreceptor protein tyrosine kinases essential for IL-2 signaling in lymphocytes. Their nucleotide sequences were 100% homologous with those expressed by lymphocytes (together they comprised 70% of the full length coding sequence). The IL-2R beta gene is constitutively expressed by AtT-20 pituitary cells, and its transcription was upregulated after CRF stimulation. Species-specific Il-2 induced intracellular signals in AtT-20 cells known to be mediated by Il-2R beta, including a transient increase in c-myc nuclear proto-oncogene transcription and the dose-dependent induction of DNA replication as measured by [3H]thymidine incorporation. The IL-2-induced DNA replication signal was not delivered by heat inactivated IL-2 and was partially blocked by a murine anti-IL-2R beta monoclonal antibody. These studies suggest that IL-2R beta may be a critical target involved in mediating the neuroimmunological actions of this prototypical cytokine in endocrine cells.
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PMID:Isolation of IL-2 receptor-beta cDNA clones from AtT-20 pituitary cells: constitutive expression and role in signal transduction. 925 80

The pituitary gland expresses cytokines and their receptors. IL-2 receptor transcripts and protein products are co-localized in ACTH-, PRL-, and GH-producing cells (double immunofluorescence). IL-2 and IL-6 (1-1000 IU/ml) are involved in the autocrine/paracrine regulation of normal and tumor (GH3 mammosomatotroph cell line and adenoma cell cultures) anterior pituitary hormone-producing cell growth (cell number, DNA synthesis, c-fos mRNA expression and autoradiography combined with hormone staining). IL-1 regulates the growth of normal pituitary cells but does not act on GH3 cells. IL-1ra, which blocks this action, is expressed in tumoral pituitary (mainly GH- and ACTH-) cells. In ACTH- cells, IL-1 enhances glucocorticoid feedback, stimulating glucocorticoid response element transcriptional activity. Cytokines, through specific functional receptors, act as inter/auto-cellular factors that regulate not only the function but also the growth of anterior pituitary cells.
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PMID:Cytokine expression and molecular mechanisms of their auto/paracrine regulation of anterior pituitary function and growth. 962 79

A somnogenic function is suspected for various cytokines. Foregoing experiments in humans indicated a selective increase in the production of interleukin-2 (IL-2) during sleep as compared with nocturnal wakefulness. Here, we examined whether conversely, IL-2 exerts a promoting influence on sleep. Also, the effects of IL-2 administered at ultra-low doses on systemic immune and endocrine parameters were assessed. Eighteen healthy men participated in three night sessions, receiving subcutaneously at 19:00 h either placebo or recombinant human IL-2 at doses of 1000 and 10,000 IU/kg bw. Polysomnographical recordings were obtained between 23:00 and 07:00 h. Blood was collected repeatedly to determine (i) white blood cell (WBC) counts including the enumeration of monocytes, natural killer (NK) cells, and lymphocyte subsets, (ii) serum concentrations of IL-2, soluble IL-2 receptor (sIL-2r), IL-4, IL-6, and interferon-gamma (IFN-gamma), and (iii) concentrations of adrenocorticotropin (ACTH), cortisol, thyreotropin (TSH), and growth hormone (GH). Changes after 1000 IU/kg bw IL-2 generally remained non-significant. However, distinct effects occurred after 10,000 IU/kg bw IL-2, inducing serum IL-2 concentrations selectively activating the high affinity IL-2 receptor. At this dose, IL-2 reduced the number of circulating lymphocytes (including all major subtypes) and NK cells, while counts of monocytes and neutrophils were increased. IL-4 release was stimulated and IFN-gamma concentration reduced after IL-2. Also, IL-2 increased the TSH concentration. There were no hints at a sleep promoting effect of IL-2. Immune changes suggest that nocturnal IL-2 administration induces a shift towards Th2 mediated defense.
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PMID:Systemic immune parameters and sleep after ultra-low dose administration of IL-2 in healthy men. 1248 Apr 97

A 66-year-old male was admitted to our hospital complaining of bilateral hypochondrial pain, back pain and loss of weight in May, 2002. Superficial lymph nodes were not palpable on admission. The leukocyte count was 3430/microl, hemoglobin concentration, 13.0g/dl, and platelet count, 174000/microl. LDH, soluble IL-2 receptor, ACTH and cortisol values were out of the normal range (LDH 1368IU/l, sIL-2R 2630U/ml, ACTH 132pg/ml, cortisol 7.4microg/dl). Abdominal CT scan showed bilateral adrenal masses, and abnormal uptake of Ga-scintigraphy was seen correspondent with the bilateral adrenal masses. The histological diagnosis of bilateral adrenal masses cannot be performed because of the bleeding tendency, but atypical cells were observed in the patient's bone marrow aspirate. Surface marker analysis of atypical cells showed CD5+, cyclin D1+, CD19+, CD20+ and HLA-DR+. From these results we diagnosed this case as a mantle cell lymphoma (stage IV B) markedly infiltrated into the adrenal glands with adrenal insufficiency. The bilateral adrenal masses dramatically reduced in size after CHOP chemotherapy with hydrocortisone supplementation. We report on the present case and summarize the reports of adrenal grand-infiltrating lymphomas.
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PMID:[Mantle cell lymphoma markedly infiltrated into adrenal glands with adrenal insufficiency]. 1535 15