Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was undertaken to investigate whether or not the endogeneous mechanisms in the brain can modulate the changes in nociception produced by peripherally-administered interleukin-1 beta (IL-1 beta) in rats. We administered diclofenac and alpha-melanocyte-stimulating hormone (alpha-MSH) into the lateral cerebroventricle (LCV) 10 min before the intraperitoneal (i.p.) injection of recombinant human IL-1 beta (rhIL-1 beta, 1 ng/kg-100 ng/kg) and then observed the changes in nociception using a hot-plate test. The i.p. injection of rhIL-1 beta (10 ng/kg and 100 ng/kg) reduced the paw-withdrawal latency without affecting the colonic temperature. The maximal reduction in the paw-withdrawal latency was observed 30 min after the i.p. injection of rhIL-1 beta at 100 ng/kg. The rhIL-1 beta (100 ng/kg)-induced hyperalgesia was inhibited by the LCV injection of both diclofenac (1 ng) and alpha-MSH (100 ng). The LCV injection of either diclofenac (1 ng) or alpha-MSH (100 ng) was found to have no effect on nociception by itself. These findings therefore suggest that the hyperalgesia induced by peripheral IL-1 beta can be modulated by a cyclooxygenase pathway of the arachidonate and alpha-MSH in the brain.
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PMID:Inhibition of peripheral interleukin-1 beta-induced hyperalgesia by the intracerebroventricular administration of diclofenac and alpha-melanocyte-stimulating hormone. 893 Mar 29

alpha-Melanocyte-stimulating hormone (alpha-MSH, alpha-melanotropin) has been shown to be an inhibitory factor in many immunologic and inflammatory processes involving the cytokine interleukin-1 (IL-1). As the mechanism of the interaction between IL-1 and alpha-MSH at the receptor level is unknown, we have studied the role of MC1 melanocortin receptors in two variants of the human melanoma cell line A375 differing in their sensitivity to the cytostatic effects of IL-1 beta. Both IL-1 sensitive (A375r-) and resistant cells (A375r+) carry specific high affinity receptors for IL-1, albeit their concentration is 10-fold higher in A375r+ cells. In A375r- cells, MC1 receptors are absent or below the level for reliable detection in the binding assay. Conversion of A375r- to A375r+ cells by prolonged culture in medium not depleted of endotoxin led to the appearance of MC1 receptors (KD 0.4 +/- 0.123 nmol/l; 608 +/- 134 receptors/cell). Stable transfection of A375r- cells with the human MC1 receptor did not, however, render them resistant to the cytostatic effect of IL-1 beta on concomitant treatment with alpha-MSH or result in the production of IL-6 on treatment with IL-1 beta. Therefore, the presence of MC1 receptors on the surface of A375 cells or their binding to alpha-MSH does not seem to be a factor in cytokine resistance or IL-6 secretion. No interaction between IL-1 beta and alpha-MSH could be demonstrated at the cellular level in this melanoma cell line.
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PMID:MSH receptors and the response of human A375 melanoma cells to interleukin-1 beta. 902 91

A number of recent studies suggest that interleukin 1 beta (IL-1 beta) is a major mediator of hypothalamo-pituitary-adrenal (HPA) responses following infectious aggression. We investigated whether IL-1 beta mediates long-term changes in HPA activity and studied the cellular regulation of the anterior pituitary. To mimic chronically elevated IL-1 beta production thought to occur during infectious diseases, osmotic pumps (Alzet type) were implanted in the peritoneal cavity of male rats and hIL-1 beta was infused continuously at rates of 1 or 3 micrograms/day. Effects of hIL-1 beta action on plasma ACTH, beta-endorphin (beta-EP) and corticosterone (CORT) secretion and on anterior pituitary (AP), ACTH and beta-EP content were followed. In addition, hypothalamic (HT) CRH mRNA and in AP, CRH receptor (CRH-Rc) mRNA, POMC nuclear primary transcript RNA, POMC nuclear intermediate processing RNA and POMC nuclear and cytoplasmic mRNA were quantified using a highly sensitive solution hybridization nuclease protection assay. Continuous infusion of hIL-1 beta stimulated the HPA axis at varying degrees. Increased HT CRH gene expression, AP POMC gene transcription, ACTH and beta-EP release occurred only during the first 3 days of the treatment. A long-lasting enhancement of ACTH and beta-EP synthesis and of POMC gene expression resulted from activated POMC gene transcription followed by an increased POMC mRNA stability and decreased POMC mRNA turnover. In the AP, stimulation of ACTH and beta-EP secretion and POMC gene transcription disappeared after continuous IL-1 beta treatment, possibly in part due to a refractory process mediated by decreased CRH-Rc gene expression in corticotropes.
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PMID:Effects of continuous infusion of interleukin 1 beta on corticotropin-releasing hormone (CRH), CRH receptors, proopiomelanocortin gene expression and secretion of corticotropin, beta-endorphin and corticosterone. 903 74

Role of the prostaglandins (PGs) in the activation of the hypothalamic-pituitary-adrenal (HPA) axis by the adrenergic agonists, corticotropin-releasing hormone (CRH) and vasopressin (VP) in rats under basal and social stress conditions was investigated. Systemic or intracerebroventricular (icv) pretreatment with indomethacin powerfully reduced the corticosterone response to ivc phenylephrine, and alpha 1-receptor agonist, significantly diminished the response to clonidine, an alpha 2-receptor agonist, but did not alter the response to isoprenaline, a beta-adrenergic agonist. Consequently, indomethacin considerably reduced the corticosterone response to noradrenaline, and alpha 1- and alpha 2-adrenergic agonist, but did not change the response to adrenaline, a predominant beta-adrenergic agonist. Thus, prostaglandins considerably mediate the HPA activity stimulated via central alpha 1- and alpha 2- but not beta-adrenergic receptors. Social crowding stress for 3 days did not affect the corticosterone response to ip or icv CRH, but drastically reduced the response to VP. In stressed rats indomethacin did not alter the corticosterone response to CRH but significantly further impaired the diminished by stress corticosterone response to VP. Neither social stress nor endogenous prostaglandins affected the responsiveness of the CRH system. By contrast, both social stress and prostaglandins considerably diminished the HPA response to VP. The above results indicate that both these neurohormone systems have a distinct mode of adaptation and interaction with PG systems during social stress. Interleukins, particularly IL-1 beta and IL-6, activate the HPA axis. Most immunological stimuli and interleukins also activate both the central and the peripheral noradrenergic systems. Activation of the HPA axis in vivo depends on the secretion of CRH, an intact pituitary and the ventral adrenergic bundle innervating the hypothalamic paraventricular nucleus. Interleukins may cross the blood-brain-barrier or be produced in the CNS to stimulate their receptors in brain structures involved in the regulation of the HPA axis.
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PMID:Role of prostaglandins in the stimulation of the hypothalamic-pituitary-adrenal axis by adrenergic and neurohormone systems. 911 24

Hemorrhage is associated with an impairment in the immune response and with increased concentrations of circulating inflammatory cytokines. The present study determined the time course and localization of alterations in circulating and tissue pro-inflammatory cytokines (TNF-alpha, IL-1-alpha and -beta) in response to fixed-pressure (40 mm Hg) hemorrhage as well as the associated hanges in circulating neurohormonal and opioid mediators. Conscious unrestrained non-heparinized male Sprague-Dawley rats (n = 24) underwent hemorrhage followed by standard resuscitation with lactated Ringer's solution. Animals were sacrificed at three time points; immediately after the hemorrhage period, at completion of resuscitation and 1.5 h after the resuscitation period. Hemorrhage resulted in marked elevations in circulating levels of TNF-alpha, which averaged 860 +/- 201 pg/ml. The levels were similarly elevated following fluid resuscitation (877 +/- 196 pg/ml) and had decreased towards baseline 1.5 h after completion of resuscitation (281 +/- 134 pg/ml). TNF-alpha was not detectable in plasma of time-matched controls. Hemorrhage elevated TNF-alpha content in spleen (25%), lung (55%) and heart (20%), and tissue content remained elevated despite resuscitation. No significant changes in tissue content of TNF-alpha were detected in the liver, kidney or brain. Circulating levels of IL1-alpha and -beta were not detectable in either the time-matched controls or hemorrhaged animals. However, statistically significant elevations in tissue content of IL-1 alpha were observed in heart, spleen, lung, gut and whole brain (15-30%). Tissue content of IL-1 beta did not change in response to hemorrhage and/or fluid resuscitation. Activation of sympathetic outflow, as evidenced by a 3- to 4-fold elevation in circulating epinephrine and norepinephrine levels, was observed immediately after hemorrhage, and was associated with a 5-fold rise in circulating beta-endorphin. These results demonstrate an early increase in tissue cytokine content following hemorrhagic shock, which is associated with elevations in circulating catecholamines and endogenous opioids, consistent with their potential modulatory role in this response.
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PMID:Early organ-specific hemorrhage-induced increases in tissue cytokine content: associated neurohormonal and opioid alterations. 932 42

We investigated the effect of acute and chronic stress on growth hormone (GH) plasma levels in rats. Acute stress was provoked by intravenous administrations of IL-1 beta and TNF-alpha. Determinations were made at 10, 30, 60, 120 and 180 min following i.v. injection of these cytokines into the caudal vein. We also investigated the chronic stress induced by hind paw injections of Freund's adjuvant. Arthritis was developed by 21 days following such injection. GH levels were studied at 7, 14 and 21 days after induction of arthritis on several blood samples which were withdrawn from tail veins, and long-term hormonal profiles (3 hours' sampling) were determined at 12.00 am, 1.30 pm and 3.00 pm. Local administration of dexamethasone and the monoclonal antibody anti-ICAM-1 were also used in arthritic rats. Following acute stress, a significant reduction of plasma GH levels has been evidenced, possibly related to the stimulation of corticotropin-releasing hormone. Following chronic stress, we demonstrated a significant increase of GH levels, which were significantly reduced by dexamethasone treatment and to a lesser extent by anti-ICAM-1 administration.
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PMID:Effect of acute and chronic inflammation on plasma growth hormone levels in rats. 940 72

Both constitutive and inducible interleukin-1 (IL-1) gene expressions have been described in the central nervous system, the former being associated with immunoreactive IL-1 neurons in human and rat hypothalami. While most studies have focused on the role of IL-1 as a mediator of pathological events in the brain, the cytokine of neuronal origin might also be involved in the regulation of physiological processes. In this study we used a previously validated technique to investigate the effects of classical neurotransmitters and the hypophysiotropic peptide corticotropin-releasing hormone (CRH) on the release of immunoreactive (ir) IL-1 beta from acute rat hypothalamic explants. We found that basal irIL-1 beta secretion is significantly inhibited by acetylcholine and histamine and increased by dopamine, while dexamethasone, IL-4 and IL-10 have no effect. Moreover, cytokine release is dose-dependently increased by CRH. Such effects of the neurotransmitters and CRH are observed in short-term incubation experiments, indicating that a pre-formed pool of hypothalamic IL-1 beta is involved. These findings also suggest that the interaction between IL-1, neurotransmitters and neuropeptides might play a role in the physiological regulation of such processes as body temperature, food intake and the control of hypothalamic-hypophyseal axes.
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PMID:The release of immunoreactive interleukin-1 beta from rat hypothalamic explants is modulated by neurotransmitters and corticotropin-releasing hormone. 942 15

During infection, bacterial products, such as lipopolysaccharide (LPS), and viral products release cytokines from immune cells. These cytokines reach the brain by several routes. Furthermore, cytokines such as interleukin-1 (IL-1) are induced in central nervous system neurons by systemic injection of LPS. These cytokines determine the pattern of hypothalamic-pituitary secretion which occurs in infection. IL-2, by stimulation of cholinergic neurons, activates neural nitric oxide synthase (NOS). The nitric oxide (NO) released diffuses into corticotropin-releasing hormone (CRH)-secreting neurons and releases CRH. IL-2 also acts in the pituitary to stimulate adrenocorticotropic hormone secretion. On the other hand, IL-1 alpha blocks the NO-induced release of luteinizing-hormone-releasing hormone (LHRH) from neurons, thereby blocking pulsatile luteinizing hormone (LH), but not follicle-stimulating hormone release, and also inhibiting sexual behavior which is induced by LHRH. IL-1 alpha and granulocyte-macrophage colony-stimulating factor (GM-CSF) block the response of the LHRH terminals to NO. GM-CSF inhibits LHRH release by acting on its receptors on gamma-aminobutyric acid (GABA)ergic neurons to stimulate GABA release. GABA acts on GABA-A receptors on the LHRH neuronal terminal to block NOergic stimulation of LHRH release. This concept is supported by a blockade of GM-CSF-induced suppression of LHRH release from medial basal hypothalamic explants by the GABA-A receptor blocker, bicuculline. IL-1 alpha inhibits growth hormone (GH) release by inhibiting GH-releasing hormone release mediated by NO and stimulating somatostatin release, also mediated by NO. IL-1 alpha-induced stimulation of prolactin release is also mediated by intrahypothalamic action of NO which inhibits release of the prolactin-inhibiting hormone, dopamine. The actions of NO are brought about by its combined activation of guanylate cyclase liberating cyclic guanosine monophosphate and activation of cyclooxygenase and lipoxygenase, with liberation of prostaglandin E2 and leukotrienes, respectively. Thus, NO plays a key role in inducing the changes in the release of hypothalamic peptides induced in infection by cytokines. Cytokines, such as IL-1 beta, also act in the anterior pituitary gland, at least in part, via induction of inducible NOS. The NO produced alters the release of anterior pituitary hormones.
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PMID:Nitric oxide controls the hypothalamic-pituitary response to cytokines. 948 1

A number of previous studies have concluded that prostaglandins (PGs) play a crucial role in mediating the corticotropin-releasing hormone and adrenocorticotropin (ACTH) secretion induced by interleukin (IL) 1 beta in the rat. This is mainly based on a significant inhibitory effect of indomethacin, a cyclooxygenase inhibitor, on the hormonal response. However, there is one previous study which reported that such an inhibitory action of indomethacin on ACTH secretion is mediated principally by a fast, rate-sensitive negative feedback effect of corticosterone which increases after indomethacin injection, rather than by a decrease in PG production. In order to have a better understanding of this unresolved issue, in the present study the authors compared the effects of two different time intervals (10 or 20 min) between the intravenous injections of indomethacin (10 mg/kg body weight) and of recombinant human IL-1 beta (3 micrograms/kg body weight) on the cytokine-induced ACTH secretion in male rats. Although IL-1 beta-induced ACTH response was significantly suppressed by indomethacin given either 10 or 20 min before, the latter protocol led to a significantly greater inhibition of the hormonal response than the former. However, between the two groups, the rising slope of corticosterone from -20 or -10 min to time zero and that from time zero to 10 min after IL-1 beta injection were statistically indistinguishable. There results strongly suggest that the fast, rate-sensitive negative feedback effect of corticosterone may not be a principal mechanism whereby indomethacin inhibits IL-1 beta-induced ACTH secretion in the rat. It was concluded that such an action of indomethacin is primarily mediated by its inherent pharmacological action, i.e. the inhibition of endogenous PG production.
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PMID:Evidence that a fast, rate-sensitive negative feedback effect of corticosterone is not a principal mechanism underlying the indomethacin inhibition of interleukin-1 beta-induced adrenocorticotropin secretion in the rat. 961 76

Although it is well established that peripheral administration of endotoxin activates the hypothalamic-pituitary-adrenal (HPA) axis, information is very limited regarding whether central administration of endotoxin can similarly stimulate the endocrine axis. Moreover, it is also unknown whether a difference exists in the mode of involvement of brain-derived cytokines in determining the HPA response to peripheral vs central administration of endotoxin. In the present study, the authors attempted to gain more knowledge on these issues focusing on interleukin (IL) 1 in the brain, one of key pro-inflammatory cytokines mediating the immuno-endocrine network. In male rats, both intravenous (i.v., 100 micrograms/kg body weight) and intracerebroventricular [i.c.v. (the 3rd ventricle), 10 micrograms] injections of Escherichia coli lipopolysaccharide (LPS) caused a significant elevation of adrenocorticotropin (ACTH) levels in plasma, even though peaked ACTH responses occurred earlier after the i.v. (60 min post-injection) than the i.c.v. (120 min post-injection) LPS. Although the ACTH response to i.c.v. LPS was significantly suppressed by a prior (5 min) i.c.v. administration of IL-1 receptor antagonist (IL-1Ra, 1 microgram), the hormonal response to i.v. LPS was not. That this dose of IL-1Ra was not biologically a small dose was indicated by another experiment that the same dose of i.c.v. IL-1Ra was able to significantly suppress the ACTH response to an i.c.v. injection of recombinant human IL-1 beta (50 ng). These results suggest that i.c.v. LPS, as i.v. LPS, can stimulate ACTH secretion in the rat, and this hormonal response may, at least in part, be mediated by brain-derived IL-1. Although there is one previous study reporting an important role of central IL-1 in mediating the HPA response to systemic LPS treatment, our present data suggest that such a mechanism may not operate before and during an early, peak phase of ACTH secretion after i.v. LPS.
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PMID:Different roles of brain interleukin 1 in the adrenocorticotropin response to central versus peripheral administration of lipopolysaccharide in the rat. 961 78


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