UNIPROT:P05231 - FACTA Search

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

In previous studies, rat adrenal zona glomerulosa (ZG) cells were demonstrated to release interleukin-6 (IL-6). In the current study, cultures of ZG cells and bioassays for tumor necrosis factor (TNF) and IL-6 were used to determine if ZG cells release TNF and to define more fully the factors that regulate ZG IL-6 release. ZG cells released IL-6 and TNF, and this release was stimulated by lipopolysaccharide, interleukin-1 alpha, interleukin-1 beta, a protein kinase C activator, and a calcium ionophore without affecting intracellular adenosine 3', 5'-cyclic monophosphate (cAMP) content. In contrast, adrenocorticotropic hormone (ACTH) increased the intracellular cAMP content, increased basal and secretagogue-stimulated IL-6 release but decreased basal and secretagogue-stimulated TNF release. The effects of ACTH on IL-6 and TNF release may be mediated by increases in intracellular cAMP because ACTH and dibutyryl cAMP modified IL-6 and TNF release in an identical manner. Therefore, IL-6 and TNF release from ZG cells can be differentially regulated. Because IL-6 and TNF modify adrenal steroid release, the adrenal production of these cytokines may have a role in the stress response.
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PMID:Differential release of tumor necrosis factor and IL-6 from adrenal zona glomerulosa cells in vitro. 784 Jan 68

The neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) has potent antipyretic and antiinflammatory properties. When administered systemically, the naturally occurring molecule and its COOH-terminal tripeptide sequence inhibit inflammation induced by peripherally applied irritants and intradermal injections of mediators of inflammation such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF alpha). We recently found that alpha-MSH can act solely within the brain to inhibit inflammation caused by a general irritant applied to the skin. This activity appears to be shared with salicylate drugs and the combined observations suggest the existence of descending neurogenic antiinflammatory signals capable of modulating inflammation in peripheral tissues. To improve our knowledge of the scope of this action of the peptide, alpha-MSH was injected into the cerebral ventricles (i.c.v.) of mice that had received intradermal injections in the ear of mediators of inflammation: IL-1 beta, IL-8, leukotriene B4, and platelet-activating factor. The centrally administered peptide inhibited the actions of all of these proinflammatory agents as determined from comparisons with measures of ear edema over time in control animals; this indicates that the central peptide can alter inflammation induced in the periphery by major mediators of inflammation. In tests confined to IL-1 beta, central administration of alpha-MSH(11-13) was also effective. These findings support the concept of a descending neurogenic antiinflammatory influence promoted by an action of alpha-MSH within the brain, an inhibitory influence that is not restricted to modulation of just one or a limited set of the mediators of inflammation.
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PMID:Central neurogenic antiinflammatory action of alpha-MSH: modulation of peripheral inflammation induced by cytokines and other mediators of inflammation. 812 2

Among vertebrates, there is an extreme conservation in amino acid sequence for the neuropeptide PACAP-38 and its C-terminal shortened derivative PACAP-27. The PACAP gene is assigned to chromosome 18 in man and its organization has been characterized. PACAP-38 and its minor derivative PACAP-27 are widely distributed in the central nervous system. PACAP-38 is particularly abundant in hypothalamus. The mapping of the afferentation and efferentation of PACAP systems are progressively delineated, including a search for the colocalization with other neurotransmitters. In several peripheral organs positive neuronal perikarya and fibers are also seen. PACAP acts through two types of receptors: (1) the highly selective type I that displays a 500 to 2000 selectivity for PACAP-38 and PACAP-27 as compared to VIP; (2) type II is the so-called VIP receptor showing similar high affinity for PACAP-38, PACAP-27 and VIP. It is less selective, therefore, than previously thought. This is why this second receptor, qualifying as an unspecific VIP-PACAP receptor, is hardly considered here. Type I receptors can stimulate two enzymes: the adenylate cyclase and phospholipase C (whose activation leads to the inositol phosphate-cytosolic Ca2+ cascade). This dual coupling may have several distal consequences including on gene expression, cell growth and differentiation. Although a relatively comprehensive spectrum of pharmacological activities has already been established we still need to limit the physiological roles of PACAP as neurotransmitter and/or neuromodulator. Concerning the hypothalamo-pituitary axis, PACAP reduces food intake in mice and raises plasma arginine vasopressin in rat, probably through PACAP-ir neurons in paraventricular and supraoptic nuclei projecting to the neurohypophysis. PACAP originating in the hypothalamus may also be transported to the anterior pituitary through portal vessels. Data on the antehypophysis suggest a role on i.a. reproduction and growth. PACAP stimulates adenylate cyclase and increases [Ca2+] in gonadotropes, somatotropes, and folliculo-stellate cells. It elevates the secretion of alpha-MSH from melanotropes, and that of interleukin-6 from pituitary folliculo-stellate cells. PACAP potentiates the effects of LHRH on LH and FSH secretion. More clearly perhaps, PACAP increases the synthesis of LH, GH, PRL and ACTH after 1-2 days. In human pathology, PACAP-27 and PACAP-38 stimulate adenylate cyclase activity in membranes from 'null'-, gonadotropin-, GH-, and ACTH-producing pituitary adenomas but are inactive in prolactinomas.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Type I receptors for PACAP (a neuropeptide even more important than VIP?). 821 37

Immune and neuroendocrine systems interact at various levels. In particular, either cytokines activate the hypothalamus-pituitary-adrenal axis (HPA) or corticotropin-releasing hormone (CRH) induces the release of beta-endorphin from peripheral human mononuclear cells. The aim of the present study was to investigate whether CRH may affect cytokine production and activity in human peripheral blood mononuclear cells (PBMC). Primary cultures of human PBMC and monocytes were used. They were incubated in presence of different doses of synthetic human CRH. Media were collected and interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) levels were measured by ELISA, while interferon-gamma (IFN-gamma) levels were measured by bioassay. In addition, phytohemoagglutinin-induced lymphocyte proliferation was evaluated by testing [3H]thymidine incorporation in the presence of various doses of CRH. CRH significantly increased IL-6 release from PBMC (p < 0.01). The addition of CRH to PBMC significantly decreased IFN-gamma levels, in a dose dependent manner (p < 0.01). No significant effect of CRH was observed on lymphocyte proliferation or IL-1 beta production. The present results suggest a role for CRH as a paracrine mediator for human immune cells, increasing the evidence of a clear correlation between immune and neuroendocrine system.
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PMID:Corticotropin-releasing hormone modulates cytokines release in cultured human peripheral blood mononuclear cells. 824 69

Fever is induced by interactions of bacterial pyrogens with cells from the immune system, which subsequently release a cascade of cytokines. After intramuscular injection of lipopolysaccharide (LPS) from E. coli, increased amounts of tumor necrosis factor (TNF) and interleukin-6 (IL-6) can be measured in blood plasma and in perfusates of the anterior hypothalamus, where body temperature is regulated. These substances are therefore candidates to be involved in the modification of thermoregulatory structures leading to the febrile rise in body temperature. This increase of body temperature is limited and sometimes even prevented by the actions of endogenous antipyretic neuropeptides like arginine vasopressin (AVP), adrenocorticotropin (ACTH) and melanocyte-stimulating hormones (MSHs) liberated within the brain or systemically during fever. For AVP, most experimental evidence confirms antipyretic pathways from the hypothalamic paraventricular nucleus to the septal area of the limbic system, which are activated during fever and by several stressful stimuli. Fever and endogenous antipyresis are interconnected and result from interactions between the immune system and the central nervous system.
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PMID:Neurobiological concepts of fever generation and suppression. 825 4

The present study compares the effects of endotoxin, a key factor in gram-negative bacterial infection, and of corticotropin-releasing hormone (CRH) on ACTH and cortisol secretion in healthy male volunteers in a placebo-controlled design. Endotoxin (isolated from Salmonella abortus equi; 0.4 ng/kg body weight) induced a significantly delayed and prolonged increase of ACTH and cortisol secretion as compared to CRH (100 micrograms), supporting the hypothesis that different intermediate mechanisms are involved (baseline/peak: ACTHEndotoxin vs. ACTHCRH: 140 +/- 40 min vs. 44 +/- 17 min (p < 0.001); CortisolEndotoxin vs. CortisolCRH: 113 +/- 51 min vs. 66 +/- 31 min (p < 0.05); peak/baseline: ACTHEndotoxin vs. ACTHCRH: 244 +/- 79 min vs. 200 +/- 25 min (p < 0.05); CortisolEndotoxin vs. CortisolCRH: 278 +/- 76 min vs. 182 +/- 16 min (p < 0.001)). Activation of the hypothalamo-pituitary-adrenocortical (HPA) system by endotoxin in men is associated with increased interleukin-6 (peak value: 124 +/- 109 pg/ml) and tumor necrosis factor-alpha (peak value: 69 +/- 53 pg/ml) plasma levels which, probably together with locally produced interleukin-1, stimulate the HPA system both at the hypothalamic and (to a lesser degree) at the pituitary site. Provided that strictly controlled laboratory conditions are applied, the endotoxin challenge test presented here may serve as an appropriate and safe tool to explore an individual's capacity for neuroendocrine adaptation to a bacterial stressor, thus providing information complementary to the CRH test.
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PMID:Endotoxin- and corticotropin-releasing hormone-induced release of ACTH and cortisol. A comparative study in men. 826 45

Alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH), peptides derived from the precursor proopiomelanocortin, share amino acid homology at the aminoterminus of ACTH, occur within the pituitary and the brain and are potent antipyretic compounds in cytokine-mediated fever. Because alpha-MSH and ACTH act within the hypothalamus to block leukocytic pyrogen- or cytokine-mediated fever, we hypothesized that these compounds might also be capable of blocking the action of interleukin-1 (IL-1) and interleukin-6 (IL-6) to stimulate corticotropin-releasing factor (CRF) release from the hypothalamus. Mediobasal hypothalami (MBH) were incubated in vitro. After 60 min preincubation in Krebs-Ringer bicarbonate buffer (KRB), MBH explants were incubated for 30 min with KRB alone or KRB containing IL-6 (10(-13) M), IL-1 (10(-16)-10(-10) M) and/or ACTH1-24 (10(-15)-10(-9) M) or alpha-MSH (10(-15)-10(-8) M); CRF release into the incubation medium was measured by RIA. None of the ACTH1-24 or alpha-MSH concentrations changed basal CRF release significantly. As we reported previously, IL-6 (10(-13) M) increased CRF release; this increase was suppressed, in a dose-dependent fashion, by alpha-MSH at concentrations of 10(-13)-10(-11) M, with the maximal inhibitory effect observed at 10(-13) M. ACTH1-24 also exerted a dose-dependent inhibitory effect on IL-6-stimulated CRF release but at even lower concentrations (10(-15)-10(-13) M) with the maximal inhibitory effect observed with the 10(-14) M concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alpha-melanocyte-stimulating hormone abolishes IL-1- and IL-6-induced corticotropin-releasing factor release from the hypothalamus in vitro. 826 64

It has been shown previously that opioids induce antinociceptive effects at peripheral sites in the presence of inflammatory processes. Besides being elicited by local injection of opioids, such effects can also be obtained by activation of intrinsic opioid mechanisms, e.g. following stress. In the present study the possible role of cytokines in this mechanism was investigated. Unilateral inflammation of the hindpaw of rats was induced by local injection of Freund's complete adjuvant. Intraplantar injection of tumor necrosis factor alpha (TNF alpha) or interleukin-6 induced a dose-dependent increase in the threshold in the paw pressure test in the inflamed but not in the non-inflamed paw. This increase was prevented by local injection of naloxone and the mu-opioid receptor specific antagonist CTOP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2) as well as by 3-E7, an universal opioid peptide antibody. In rats pretreated with cyclosporin A to suppress the immune system, the antinociceptive effect of TNF alpha was completely inhibited. In concert with previous studies these data indicate that the tested cytokines release opioid peptides (e.g. beta-endorphin and/or enkephalins) from immune cells of the inflamed tissue which act on opioid receptors present on sensory nerve terminals, resulting in antinociception.
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PMID:Peripheral mechanisms of opioid antinociception in inflammation: involvement of cytokines. 828 87

Interleukin-6 (IL-6) and alpha-melanocyte-stimulating hormone (alpha MSH) are important modulators of the immunologic response to tissue injury and antigenic challenge. Serial changes in the plasma concentrations of these two peptides were measured in 12 patients undergoing heart transplantation. Tissue concentrations of IL-6 in atrial samples from both donor and recipient hearts were also compared. Plasma IL-6 concentration remained stable prior to cardiopulmonary bypass (CPB), initially decreased with the onset of CPB, and then increased significantly over control values at the end of CPB (180 +/- 40 v 53 +/- 60 pg/mL). Plasma IL-6 remained elevated for at least 60 minutes after CPB, and then it returned to control values by 24 hours postoperatively (67 +/- 9 pg/mL). Examination of IL-6 changes after CPB in 10 additional patients undergoing nontransplant cardiac surgery with CPB revealed a similar elevation in IL-6 at 60 minutes after CPB (290 +/- 76 pg/mL). However, IL-6 in the nontransplant group remained significantly elevated at 24 hours (138 +/- 42 pg/mL). These combined results suggest that CPB causes a marked increase in IL-6, and that implantation of a new heart in transplant patients does not augment this increase. The return of IL-6 to control values by 24 hours in the patients who have had transplants suggests that immunosuppression has an appreciable effect on IL-6 at this time. In contrast to IL-6, plasma alpha MSH never increased above control values.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Perioperative measurements of interleukin-6 and alpha-melanocyte-stimulating hormone in cardiac transplant patients. 838 85

Systemic administration of human interferon-alpha stimulates the pituitary-adrenal axis in men, but the exact mechanism still remains to be established. The present study was undertaken to examine the hypothesis that interferon-alpha may alter the circulating concentrations of the cytokines which involve the activation of the pituitary-adrenal axis. Eleven patients with chronically active hepatitis C were treated with human lymphoblastoid interferon-alpha (IFN: 6 x 10(6) IU/day) and changes in plasma adrenocorticotropin (ACTH), serum cortisol and cytokine concentrations were observed on both the first and second days of the treatment. Subcutaneous administration of IFN significantly increased plasma ACTH and serum cortisol concentrations by 3 h after the injection. Serum interleukin-6 (IL-6) increased with the increase in circulating ACTH and cortisol. There was a significant correlation between serum cortisol and IL-6 concentrations at 3 h. In contrast, an increase in serum interleukin-1 beta was only observed in one case. On the second day of IFN treatment, simultaneous administration of 25 mg diclofenac sodium eliminated the IFN effects on circulating ACTH, cortisol and IL-6 concentrations. The present studies demonstrated that circulating IL-6 increases after systemic IFN administration, resulting in activation of the pituitary-adrenal axis.
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PMID:Increase in serum interleukin-6, plasma ACTH and serum cortisol levels after systemic interferon-alpha administration. 855 63

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