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

It has previously been shown that the cytokines interleukin-1 beta and interleukin-6 (IL-1 beta and IL-6) stimulate directly the release of corticotrophin-releasing-hormone-41 from the rat hypothalamus in vitro, while IL-1 beta can also stimulate the release of somatostatin. These effects can be antagonized by drugs which block prostaglandin (PG) synthesis. PGs are also involved in the control of hypothalamic neuropeptides by other neurotransmitters. In the present study, we have characterized the production of PGs from the rat hypothalamus in vitro, and investigated the effects of IL-1 beta and IL-6, as well as the neurotransmitters norepinephrine, acetylcholine and 5-hydroxytryptamine, on the acute release of PGs, using a well-validated acute hypothalamic incubation system. The rate of release of PGs [PGE2, PGF2 alpha, 6-keto-PGF1 alpha (6KPGF1 alpha) and thromboxane B2 (TXB2) in the medium was found to stabilize after 60 min of preincubation and thereafter remain constant, with TXB2 being the predominant species. Twenty-minute incubation in the presence of human recombinant IL-1 beta or IL-6, in the dose range 1-100 U/ml, had no effect on the release of PGF2 alpha, 6KPGF1 alpha or TXB2; however, the release of PGE2 was significantly increased by both IL-1 beta and IL-6. The effect of IL-1 beta was antagonized by both indomethacin and dexamethasone. None of the other neurotransmitters tested had any effect on the release of any of the PGs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-1 beta and interleukin-6 specifically increase the release of prostaglandin E2 from rat hypothalamic explants in vitro. 164 Oct 74

There is clear evidence for communication between the immune and neuroendocrine systems. However, the effect of cytokines as major immune mediators on the hypothalamic growth peptides, GHRH and somatostatin (SRIH), is not well established. To investigate a possible hypothalamic action of the cytokines interleukin-1 beta (IL-1), interleukin-6, and tumor necrosis factor-alpha, on the release of GHRH and SRIH, we used a previously validated acute rat hypothalamic explant system. IL-1 caused a pronounced dose-dependent stimulation of SRIH in the dose-range 1-100 U/ml (P less than 0.01). GHRH showed a slight, but significant, increase in response to IL-1 tested in the dose-range 10-100 U/ml. Similar studies with mediobasal hypothalamic (GHRH and SRIH) or median eminence (SRIH) fragments produced no change in either GHRH or SRIH release. The effects of IL-1 were antagonized by the cyclo-oxygenase inhibitor, indomethacin (10 micrograms/ml). Stimulation of GHRH and SRIH could not be blocked by the CRH-antagonist alpha-helical CRH (9-41) at 10(-6) M. Interleukin-6, in the dose range 10-100 U/ml, and tumor necrosis factor-alpha, in the dose range 10-10,000 U/ml, had no effect on the acute hypothalamic release of either GHRH or SRIH. It is concluded that IL-1 stimulates the acute hypothalamic release of GHRH and SRIH, and that this effect is mediated by cyclo-oxygenase products. The marked IL-1 stimulation of hypothalamic SRIH release may override the minor increase of GHRH increase, and may thus contribute to disturbances in growth seen in the presence of chronic inflammation.
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PMID:Interleukin-1 beta modulates the acute release of growth hormone-releasing hormone and somatostatin from rat hypothalamus in vitro, whereas tumor necrosis factor and interleukin-6 have no effect. 167 97

Interleukin-6 (IL-6) is an inflammatory cytokine that stimulates T-cell activation and B-cell differentiation. We recently reported that picomolar concentrations of IL-6 stimulated PRL, GH, and LH release in vitro. These data suggested that IL-6 may function as a hypothalamic releasing factor for anterior pituitary hormones. Medial basal hypothalami (MBH) were incubated for 60-90 min in Krebs-Ringer bicarbonate buffer supplemented with 0.025% BSA, and the conditioned medium was assayed for IL-6 concentrations by the 7TD1 cell growth factor assay. It was found that MBH released IL-6 in vitro. Although depolarizing concentrations of K+ (56 mM) did not increase IL-6 release, somatostatin release from the MBH was increased significantly. The bacterial endotoxin lipopolysaccharide (LPS; 1-100 ng/ml) induced significant increases in IL-6 release from the MBH. The presence of IL-6 in the hypothalamus suggested a possible role for this cytokine in the regulation of neuropeptide release; however, the release of somatostatin was not affected by 20 ng/ml IL-6. Comparison studies of neural and neuroendocrine tissues revealed that the anterior and posterior pituitaries released larger amounts of bioactive IL-6 than the MBH or parietal cortex during a 4-h incubation; induction of IL-6 release by endotoxin occurred only in the anterior pituitary and hypothalamus. IL-6 mRNA was detectable in the MBH and anterior pituitary tissue after a 4-h incubation; however, no IL-6 mRNA was detectable in freshly isolated tissues. LPS (100 ng/ml) and (Bu)2cAMP (1 mM) increased IL-6 mRNA accumulation in and IL-6 release from the MBH and anterior pituitary. These data suggest that the MBH synthesizes and releases IL-6 via a nonneuronal source in vitro.
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PMID:Endotoxin-induced release of interleukin-6 from rat medial basal hypothalami. 197 93

Inflammatory states are associated with nervous and neuroendocrine responses, which appear to be mediated through the actions of cytokines. Since endotoxin treatment in the rat is associated with declines in thyrotropin (TSH) secretion and growth hormone (GH) secretion, changes that may be explained by stimulation of hypothalamic somatostatin (SRIF), the effects of cytokines on SRIF were examined. In an in vitro model system consisting of fetal rat diencephalic cells interleukin-1 (IL-1), tumor necrosis factor (TNF) and interleukin-6 (IL-6) were found to stimulate the synthesis and release of SRIF. This effect developed slowly over 24 hours and was dose- and time-dependent. Acute release of SRIF over periods up to 1 hour was not found. The mechanism of cytokine stimulation of SRIF is not known. Since the depletion of glial cells in the cultures inhibits the effect, mediators that depend on the presence glia may be involved. The ability of cytokines to stimulate brain SRIF is likely to prove relevant to our understanding in many areas, including brain development, brain responses to injury, and neuroendocrine changes in chronic illness.
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PMID:Somatostatin regulation by cytokines. 197 2

Using a functioning rat thyroid cell line (FRTL-5), we examined the effects of some cytokines, particularly interleukin-1 (IL-1) on the growth of thyroid cells. In 5H medium, namely Coon's modified Ham's F-12 medium supplemented with 5% calf serum and a five-hormone preparation consisting of insulin, hydrocortisone, transferrin, glycyl-L-histidyl-L-lysine acetate and somatostatin, IL-1 enhanced the growth of FRTL-5 cells detected by [3H]TdR incorporation. However, in 6H medium (5H medium plus bovine TSH), IL-1 inhibited the growth of FRTL-5 cells. Both effects were neutralized by the addition of anti-IL-1 antibody. Furthermore, IL-1 inhibited the growth of FRTL-5 cells induced by forskolin which is known as an adenylate cyclase activator. FRTL-5 cells have specific IL-1 receptors detected by the binding of 125I-labeled IL-1 alpha. By Scatchard plot analysis, the numbers and the dissociation constants of IL-1 receptors on FRTL-5 cells were shown to be 5225/cell and 8.69 x 10(-10) M. Interleukin-2, interleukin-6 and interferon-gamma (IFN-gamma) had no significant effects on the cell growth in 6H medium, while IFN-gamma and insulin-like growth factor I stimulated cell growth somewhat in 5H medium. These results suggest that IL-1 plays a regulatory role in the growth of thyroid cells through binding to the IL-1 receptors.
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PMID:Inhibitory effect of IL-1 on the TSH dependent growth of rat thyroid cells (FRTL-5). 212 71

Interleukin-6 (IL-6) is an inflammatory cytokine that is produced by a variety of cells and tissues. We recently demonstrated that IL-6 is produced by anterior pituitary cells in response to the bacterial endotoxin lipopolysaccharide and phorbol diester in vitro. Lipopolysaccharide (0.01-100 ng/ml) increased, whereas dexamethasone (0.1-100 nM) decreased, IL-6 production by anterior pituitary cells in vitro as measured by the 7TD1 cell growth factor assay. In addition, we now report that IL-6 production by anterior pituitary cells is stimulated by agents that elevate intracellular cAMP concentrations. Exposure of anterior pituitary cells to (Bu)2cAMP (0.01-10 mM), prostaglandin E2 (1.0-1000 nM), forskolin (50-1000 nM), or cholera toxin (0.25-250 ng/ml) for 6 h resulted in concentration-related increases in the production of IL-6, which, in the cases of forskolin and cholera toxin, correlated well with increased intracellular cAMP concentrations. Vasoactive intestinal peptide (1-1000 nM), which stimulates adenylate cyclase activity in the anterior pituitary, caused a concentration-related enhancement of IL-6 production that was unaffected in the presence of 10-100 nM somatostatin. In contrast, GH-releasing factor had no effect on IL-6 production. These data suggest that anterior pituitary cells produce IL-6 in response to increased intracellular cAMP, and that the neuropeptide vasoactive intestinal peptide may act to regulate IL-6 production.
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PMID:Production of interleukin-6 by anterior pituitary cells is stimulated by increased intracellular adenosine 3',5'-monophosphate and vasoactive intestinal peptide. 216 22

Recent evidence has revealed that various neuropeptides appear to have distinct roles as immunomodulators. The aim of this study was to evaluate the role of hypothalamic neuropeptides (thyreoliberin [TRH], somatostatin [SRIF], and gonadoliberin [LH-RH]) on the secretion of interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) from lipopolysaccharide (LPS) activated human peripheral blood monocytes (PM) cultured in vitro. LPS in concentration 1.5 micrograms/ml stimulated PBM to release IL-1 beta or IL-6 into the supernatants. SRIF in concentrations from 10(-8)M to 10(-10)M (but neither RH nor LH-RH in the same concentrations) potentiated the release of IL-6 from PBM. None of the tested neuropeptides stimulated the release of IL-1 beta from LPS activated human monocytes. These data indicate that SRIF in physiological or pharmacological concentrations which activate the release of IL-6 from PBM may be one of the regulators of immune response in humans.
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PMID:Somatostatin (SRIF) stimulates the release of interleukin-6 (IL-6) from human peripheral blood monocytes (PBM) in vitro. 747 64

Interleukin-1, tumor necrosis factor, and interleukin-6 inhibit insulin release and may be cytotoxic to isolated pancreatic islets. These cytokines have been postulated to play an important role in the beta cell destruction characteristic of type 1 diabetes. The present study was designed to investigate the effect of the above cytokines on insulin, glucagon, somatostatin, and thyrotropin-releasing hormone secretion by isolated human islets. In addition, we have investigated if cytokine-induced modifications in hormone secretion are accompanied by modifications in the ab initio synthesis of any specific lipidic fraction. All three cytokines studied, although not modifying insulin and somatostatin release to glucose 5 mmol/L, inhibited the response of both hormones to glucose 20 mmol/L. On the other hand, the cytokines almost completely blocked islet basal glucagon release, without affecting thyrotropin-releasing hormone secretion. The added cytokines also suppressed 20 mmol/L [U-14C]glucose incorporation into both phospholipids and diacylglycerol. Our results demonstrate a beta-, alpha-, and delta-cell, sensitivity to cytokine action. Additionally, they suggest that ab initio lipid synthesis might be implicated in the mechanism of insulin release in human islets.
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PMID:Cytokine-induced inhibition of lipid synthesis and hormone secretion by isolated human islets. 802 53

The junB gene is one of immediate-early genes whose expression are regulated by a variety of extracellular stimuli and play important roles in cellular responses to the given stimuli. Interleukin-6 (IL-6) activates the junB promoter through an IL-6 response element, JRE-IL6, that is composed of two cooperative DNA motifs, a low affinity Stat-binding site overlapping with an Ets-binding site (JEBS) and a cAMP responsive element (CRE)-like site. This element is a target for the Jak-Stat signal transduction pathway. We showed that IL-6 induced novel complexes on JRE-IL6, termed JRE-IL6-BC1 and 2, which contained Stat3 but migrated more slowly than the complexes containing homo- or heterodimer of Stat3 and Stat1 in gel shift assays. These slow-migrating JRE-IL6-BCs appeared to contain CRE-like site binding proteins besides Stat3, since the formation of JRE-IL6-BCs required both the JEBS and CRE-like site of JRE-IL6 and oligonucleotides containing the CRE-like site or somatostatin CRE efficiently competed with JRE-IL6 for making JRE-IL6-BCs. The formation of the complexes correlated well with the responsiveness of JRE-IL6 to IL-6 signals. U.v.-cross linking study revealed that JRE-IL6 bound a 90 kDa protein, corresponding to Stat3, and a 36 kDa protein, most likely a CRE-like site binding protein(s). Furthermore, we showed that the IL-6/interferon gamma (IFN gamma) response element in the IRF-1 promoter (IR/IRF-1), which contains a Stat-binding site and an adjacent CRE-like site, also makes IL-6-induced binding complexes similar to JRE-IL6-BCs.
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PMID:IL-6-inducible complexes on an IL-6 response element of the junB promoter contain Stat3 and 36 kDa CRE-like site binding protein(s). 863 11

Somatostatin and its analogs can inhibit growth in several cell types, in part by interfering with insulin-like growth factor-I (IGF-I) signaling. Our previous studies point to the importance of paracrine and autocrine IGF-I in the support of growth and survival of human multiple myeloma (MM) cell lines. In this report, we have investigated the potential role of a somatostatin analog, octreotide, in regulating growth and/or survival in MM. The results show that all MM cell lines express functional somatostatin receptors (sst). The MM cell lines express the subtypes sst2, sst3, and predominantly sst5 as determined by reverse-transcriptase polymerase chain reaction and fluorescence-activated cell sorter analysis. Octreotide inhibited the growth of both the interleukin-6 (IL-6)-dependent and the IL-6-independent MM cell lines. The effect is mainly cytostatic, resulting in 25% to 45% growth inhibition, and in three of eight of the MM cell lines a weak induction of apoptosis was recorded. Our results also show that octreotide may act as an inducer of apoptosis in primary B-B4(+) plasma cells isolated from bone marrow of MM patients. In conclusion, the results show a novel pathway for growth inhibition of MM cells: the activation of somatostatin receptor signaling.
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PMID:The somatostatin analog octreotide inhibits growth of interleukin-6 (IL-6)-dependent and IL-6-independent human multiple myeloma cell lines. 1002 2


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