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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cytokines interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha are known to be potent effectors of ACTH secretion. Some of the peripheral effects of IL-1 beta appear to be related to the secretion of IL-6 induced by IL-1 beta. Thus, we evaluated the effect of IL-6 on ACTH secretion and its interaction with IL-1 beta. Rats received recombinant human (rhIL-6) or murine (rmIL-6) IL-6 through indwelling jugular cannulae. rhIL-6 (200 ng or 2 micrograms/rat) produced peak plasma ACTH levels which were 3- to 4-fold greater than basal levels. rmIL-6 produced similar responses. Neither species of IL-6 affected plasma prolactin levels. Comparison of rhIL-1 beta (200 ng) to rhIL-6 (200, 100 or 50 ng) showed that IL-6 elevated ACTH in a dose-dependent manner and that IL-1 beta was significantly more effective. IL-1 beta was also administered concomitantly with or 10 min after IL-6. Delivered together, IL-1 beta (100, 30 or 10 ng) and IL-6 (100 ng) produced significantly higher ACTH levels than when given alone. This additivity was also evident when IL-6 was given 10 min prior to IL-1 beta. The coadministration of IL-6 (2 micrograms) with corticotropin-releasing factor (CRF, 1 micrograms/kg, b.w.) also had an additive effect on ACTH secretion (at 20 min: 300 +/- 40 pg/ml for CRF; 320 +/- 83 pg/ml for IL-6; and 540 +/- 44 pg/ml for CRF + IL-6), whereas a higher dose of CRF (10 micrograms/kg b.w.) yielded ACTH levels of 1,000 +/- 107 pg/ml at 20 min, with no further enhancement by IL-6. Incubation of pituitary cells with IL-6 alone (0.1, 1.0 or 3.0 nM) produced a slight but significant stimulation of ACTH secretion within 2 h in response to the higher doses of IL-6 only (p < 0.05), but did not modify the effect of CRF in vitro. To determine if the action of IL-6 was at a site(s) within the brain, IL-6 (30 or 100 ng/0.5 microliters) was injected into the third cerebroventricle of alert rats. 100 ng IL-6 elicited peak plasma ACTH levels (300 +/- 65 pg/ml) within 30 min; these were significantly higher than the buffer responses (90 +/- 25 pg/ml, p < 0.01), and lower than the responses to 30 ng IL-1 beta (530 +/- 50 pg/ml, p < 0.001). 30 ng IL-6 was ineffective.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A central mechanism is involved in the secretion of ACTH in response to IL-6 in rats: comparison to and interaction with IL-1 beta. 133 54

Here, we report that emotional stressors (restraint, footshock) can affect humoral immune responses as well as the capacity of immune and accessory cells to secrete interleukins. Acute restraint stress (5 min) caused a 4- to 6-fold enhancement of splenic antibody responses to sheep red blood cells. In an attempt to study endocrine mechanisms, we administered antibodies raised in rats to corticotropin releasing factor (CRF). Intravenous administration of these antibodies prior to stress-exposure and immunization prevented the stress-induced increase in the humoral response. In a parallel experiment, we observed that CRF-immunoneutralization prevented the restraint stress-induced increase in plasma ACTH concentrations, but was without effect on plasma prolactin, melanocyte stimulating hormone, adrenaline and noradrenaline responses. These data suggest the presence of an indirect pathway involving ACTH and related peptides by which CRF controls humoral responses to stress. A pathway involving a direct mechanism of CRF at the level of the immune cells will be discussed. In a set of other experiments, we addressed the question of whether interleukin-1 and interleukin-6 plasma levels induced by injection of endotoxin could be modulated by emotional stress. Exposure to prolonged footshock stress (20 min) prior to endotoxin injection resulted in a blunted plasma ACTH and interleukin-1 response, without affecting the endotoxin-induced plasma interleukin-6 response. These data suggest that at least one level at which emotional stress may influence immune function is by changing the capacity of immune cells to produce and/or secrete immune regulatory interleukins.
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PMID:Neuroendocrine and immunological mechanisms in stress-induced immunomodulation. 165 88

Interleukin-6 (IL-6) is a pleiotropic cytokine exerting many immunological and non immunological actions. The cytokine binds to a specific receptor, whose activation induces the association with a novel transducer, the glycoprotein gp 130. Here we present our results about the effect of IL-6 on both hormone secretion and second messenger systems at pituitary level, and the production of IL-6 from cells of central nervous system. IL-6 inhibited basal, VIP and TRH-stimulated prolactin (PRL) secretion from single lactotropes, studied by means of reverse hemolytic plaque assay, whereas in primary cultures of anterior pituitary cells, according to the literature, the cytokine stimulated prolactin secretion. IL-6 did not affect basal adenylate cyclase activity, inositol phosphate production, and cytosolic calcium concentration. Conversely, the preincubation of pituitary cells with interleukin-6 for 20 min significantly reduced VIP- and forskolin-stimulated adenylate cyclase activity, as well as inositol phosphate production and free cytosolic calcium increase induced by TRH.
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PMID:Role of interleukin-6 in the neuroendocrine system. 166 73

The effects of interferon-alpha, interferon-beta 1 and interferon-gamma on the secretions of prolactin (PRL) and interleukin-6 by primary cultured rat anterior pituitary cells were examined. These three interferons caused dose-dependent increases in PRL secretion within 30 min, and dose-dependent stimulation of interleukin-6 were weaker than the effects of interleukin-1 and tumor necrosis factor-alpha. These results suggest that interferons regulate PRL secretion from the pituitary gland, and that there may be a pathway in which interferons stimulate PRL secretion through interleukin-6 release.
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PMID:The interferon family stimulates the secretions of prolactin and interleukin-6 by the pituitary gland in vitro. 172 85

Interleukin-6 was found to be secreted from seven out of ten human pituitary tumours cultured in vitro. These tumours included prolactin-secreting, growth hormone-secreting and clinically non-functioning adenomas. The amount of Interleukin-6 secreted was variable from 58 to 10,000 units per ml. in medium removed after a four-day incubation under basal conditions. Four tumours secreted IL-6 in excess of 500U/ml, three of which were clinically non-functioning, but each secreted follicle stimulating hormone in vitro. This is the first report of a cytokine growth factor being released basally by human pituitary tumours.
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PMID:Interleukin-6 secreting human pituitary adenomas in vitro. 190 49

Tumor necrosis factor-alpha (TNF-alpha) is secreted by activated monocytes and other immune cells. This paper reports studies on the effects of TNF-alpha on the releases of pituitary hormones such as luteinizing hormone (LH), follicle-stimulating hormone, prolactin (PRL) and adrenocorticotropic hormone (ACTH). The addition of recombinant human TNF-alpha (rTNF-alpha) to cultures of pituitary cells resulted in significantly increased releases of gonadotropins, PRL, and ACTH for up to 30 min, but not later. rTNF-alpha, like GnRH, also stimulated the release of bioactive LH. In addition, rTNF-alpha induced production of an interleukin-6 (IL-6)-like molecule by pituitary cells. As IL-6 induces the releases of multiple hormones from pituitary cells, our data suggest that rTNF-alpha may stimulate the releases of multiple pituitary hormones through IL-6 production as well as by its direct action on pituitary cells.
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PMID:Induction by tumor necrosis factor-alpha of rapid release of immunoreactive and bioactive luteinizing hormone from rat pituitary cells in vitro. 217 54

Lymphokine and hematopoietic growth factors control the differentiation and proliferation of diverse cell types by binding to specific cell-surface receptors. Strikingly, the recently elucidated sequences of the interleukin-6 and erythropoietin receptors, and the interleukin-2 receptor beta-chain (p75), display a significant evolutionary resemblance of their extracellular domains. This homology extends to the binding domains of the growth hormone/prolactin class of receptors. Alternatively, little similarity exists between the cytoplasmic extensions of these diverse receptors. I discuss the evolutionary and functional implications of this broad, mosaic receptor relationship, with particular reference to possible structural resemblances between the cognate growth factors.
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PMID:A novel family of growth factor receptors: a common binding domain in the growth hormone, prolactin, erythropoietin and IL-6 receptors, and the p75 IL-2 receptor beta-chain. 255

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

Interleukin-2 (IL-2) is a pluripotential cytokine that, besides its role in the regulation of immunocompetent cells function, also stimulates hormone secretion. On the other hand, several factors, including cytokines (interleukin-1, IL-1; interleukin-6, IL-6) and pituitary hormones (thyrotropin, TSH; prolactin, PRL), exert stimulatory effects on T-cell connected IL-2 production. In order to evaluate the role of both pituitary hormones in the activation of the immune system, the following two standard diagnostic tests were performed: TRH test (0.2 mg) in 8 healthy human subjects (4F/4M) aged 18-50 years, and oral metoclopramide (MCP) test (10 mg) in 8 females with galactorrhea and regular menstruation aged 18-52 years. The mobilization (peak response) of PRL, TSH, triiodothyronine (T3), thyroxin (T4), IL-1 beta, IL-2, IL-6 in TRH test, and PRL, IL-1 beta, IL-2, IL-6 for MCP test were evaluated. The responses of TSH (2.0 +/- 0.3 vs 12.3 +/- 2.2 microlU/ml, p < 0.01), PRL (15.3 +/- 2.3 vs 46.4 +/- 8.8 ng/ml, p < 0.01), T3 (178.0 +/- 16.4 vs 248.7 +/- 21.1 ng/dl, p < 0.001), T4 (7.9 +/- 0.4 vs 9.6 +/- 0.5 micrograms/dl, p < 0.001), and IL-2 (45.6 +/- 7.8 vs 79.9 +/- 16.4 fmol/ml, p < 0.05) in TRH test were noted. The peak response of PRL (16.3 +2- 2.6 vs 107.7 +/- 22.4 ng/ml, p < 0.01) in MCP test was also observed, but without any changes in interleukin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased interleukin-2 levels during standard TRH test in man. 781 86

Mammary gland factor (MGF) is a transcription factor discovered initially in the mammary epithelial cells of lactating animals. It confers the lactogenic hormone response to the milk protein genes. We reported recently the isolation of the cDNA encoding MGF. MGF is a novel member of the cytokine-regulated transcription factor gene family. Members of this gene family mediate interferon alpha/beta and interferon gamma induction of gene transcription, as well as the response to epidermal growth factor and interleukin-6, and have been named signal transducers and activators of transcription (Stat). The name Stat5 has been assigned to MGF. We studied the mechanisms involved in the prolactin activation of Stat5 in COS cells co-transfected with cDNA encoding Stat5 and the prolactin receptor. Prolactin treatment of the transfected cells caused activation of Stat5 within 5-10 min. This activation does not require ongoing protein synthesis. Tyrosine kinase inhibitors prevent Stat5 activation in transfected COS cells. Treatment of recombinant Stat5 with a tyrosine-specific protein phosphatase in vitro abolishes its DNA binding activity. Prolactin stimulation of transfected cells induces Stat5 phosphorylation on tyrosine. Phosphorylation of in vitro transcribed and translated Stat5 with the Jak2 tyrosine kinase, but not with fyn, lyn or lck, confers DNA binding activity. The prolactin response of the beta-casein milk protein gene promoter can be observed in COS cells transfected with cDNA vectors encoding Stat5 and the long form of the prolactin receptor. The short form of the prolactin receptor is unable to promote Stat5 phosphorylation and confer transcriptional induction in COS cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prolactin induces phosphorylation of Tyr694 of Stat5 (MGF), a prerequisite for DNA binding and induction of transcription. 792 80


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