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)

To extend the knowledge on the central effects of cytokines, we studied the effects of tumor necrosis factor alpha and interleukin-1 alpha on nociceptive thresholds and spontaneous locomotor activity in rats. After central administration, both tumor necrosis factor alpha and interleukin-1 alpha significantly (P < 0.001) increase the nociceptive thresholds as measured by the hot-plate test. Tumor necrosis factor alpha, but not interleukin-1 alpha decreases spontaneous locomotor activity evaluated by the Animex test. The increase in nociceptive thresholds induced by tumor necrosis factor alpha or interleukin-1 alpha is not affected by the opiate receptor antagonist naloxone, or antisera against the endogenous opioids beta-endorphin, met-enkephalin or dynorphin. The analgesic effect of tumor necrosis factor alpha is completely antagonized by anti-IL-1 antibodies. Moreover, the cyclooxygenase inhibitor indomethacin does not antagonize the increase of nociceptive thresholds induced by either cytokine.
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PMID:Central effects of tumor necrosis factor alpha and interleukin-1 alpha on nociceptive thresholds and spontaneous locomotor activity. 130 May 7

Primary responsibility for the induction of various acute phase reactions has been ascribed to interleukin 1 (IL-1), tumor necrosis factor (TNF), or IL-6, suggesting that these cytokines may have many overlapping activities. Thus, it is difficult to identify the cytokine primarily responsible for a particular biologic effect, since IL-1 and TNF stimulate one another, and both IL-1 and TNF stimulate IL-6. In this work, the contribution of IL-6 in radioprotection, induction of adrenocorticotropic hormone (ACTH), and induction of hypoglycemia was assessed by blocking IL-6 activity. Administration of anti-IL-6 antibody to otherwise untreated mice greatly enhanced the incidence of radiation-induced mortality, indicating that like IL-1 and TNF, IL-6 also contributes to innate resistance to radiation. Anti-IL-6 antibody given to IL-1-treated or TNF-treated mice reduced survival from lethal irradiation, demonstrating that IL-6 is also an important mediator of both IL-1- and TNF-induced hemopoietic recovery. A similar IL-1/IL-6 interaction was observed in the case of ACTH induction. Anti-IL-6 antibody blocked the IL-1-induced increase in plasma ACTH, whereas recombinant IL-6 by itself did not induce such an increase. Anti-IL-6 antibody also mitigated TNF-induced hypoglycemia, but did not reverse IL-1-induced hypoglycemia. It is, therefore, likely that TNF and IL-1 differ in their mode of induction of hypoglycemia. Our results suggest that an interaction of IL-6 with IL-1 and TNF is a prerequisite for protection from radiation lethality, and its interaction with IL-1 for induction of ACTH.
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PMID:Role of interleukin 6 (IL-6) in protection from lethal irradiation and in endocrine responses to IL-1 and tumor necrosis factor. 131 Oct 16

The production of IL-1 and IL-6 by pituitary cells has recently been demonstrated. In this study we investigated the expression of IL-2 and its receptor (IL-2R) by pituitary cells of different species. In Northern blots, a single hybridizing band of 1 kb, identical to that in normal stimulated lymphocytes, was obtained with specific IL-2 probes. In the mouse AT-20 pituitary tumor cell line, IL-2 mRNA expression was detected after stimulation with corticotropin-releasing hormone or phorbol myristate acetate. In human corticotrophic adenoma cells, basal IL-2 mRNA expression as well as IL-2 secretion were further stimulated by phorbol myristate acetate. Both adenoma and AtT-20 cells showed detectable amounts of IL-2R mRNA and by immunofluorescence, IL-2R membrane expression. In addition, dual immunofluorescence studies in rat anterior pituitary cells demonstrated colocalization of IL-2R with ACTH-positive cells and other cell types expressing the receptor. In addition to the action of lymphocyte-produced IL-2, this cytokine may have a paracrine or autocrine regulatory role within the pituitary. It remains to be established whether IL-2 production occurs in the normal pituitary or is intrinsic to the process of tumor development of these cells. IL-2 may be involved in the growth control of pituitary cells.
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PMID:Interleukin-2 and interleukin-2 receptor expression in human corticotrophic adenoma and murine pituitary cell cultures. 133 Nov 77

The pattern of expression of at least four neuropeptides contained in adrenomedullary chromaffin cells is altered by exposure to the cytokines interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF alpha), alone or in combination with stimulation of other second messenger pathways. Vasoactive intestinal polypeptide (VIP) was elevated 2- to 3-fold by 1 nM IL-1 alpha within 48 h of exposure, while neurotensin and substance P synthesis were unaffected, and met-enkephalin levels were decreased 25-35%. Stimulation of VIP and substance P biosynthesis by forskolin was markedly enhanced by IL-1 alpha, while forskolin stimulation of enkephalin and neurotensin biosynthesis was unaffected. IL-1 alpha amplified the effect of phorbol myristate acetate to increase the VIP content of chromaffin cells, but antagonized phorbol ester-induced elevation of neurotensin levels. TNF alpha also demonstrated a neuropeptide-specific pattern of modulation of second-messenger effects on chromaffin cell neuropeptide levels similar to those seen with IL-1 alpha. The neuroendocrine actions of IL-1 alpha described above, unlike IL-1 action in the immune system, do not appear to be mediated through IL-2 as this cytokine did not affect VIP or enkephalin expression in the presence or absence of protein kinase stimulation. Neither IL-1 alpha nor TNF alpha affected the calcium-coupled stimulation of neuropeptide secretion and biosynthesis that occurs in response to cell depolarization in these and other neuroendocrine cells in vitro and in vivo. These data provide a functional demonstration of IL-1 and TNF receptors in chromaffin cell cultures and suggest a physiological role for cytokine production in the adrenal medulla. Since both the magnitude and direction of neuropeptide synthesis modulation by IL-1 alpha and TNF alpha are highly peptide-specific, it appears that these cytokines do not merely augment second messenger pathways that affect neuropeptide synthesis, but potentially regulate the activity of factors controlling the pattern of neuropeptide gene expression in chromaffin cells.
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PMID:Interleukin-1 alpha and tumor necrosis factor-alpha differentially regulate enkephalin, vasoactive intestinal polypeptide, neurotensin, and substance P biosynthesis in chromaffin cells. 137 39

1. The effect of alpha-melanocyte-stimulating hormone (alpha-MSH) on changes in body temperature and plasma levels of prostaglandin E2 (PGE2) were measured in the rabbit following intravenous injection of bacterial lipopolysaccharide (LPS), rabbit endogenous pyrogen (EP), human recombinant tumour necrosis factor-alpha (TNF-alpha), human recombinant interleukin-1 beta (IL-1 beta) and intracerebroventricular injection of PGE2. 2. LPS (25 ng kg-1), EP (25 microliters kg-1), TNF-alpha (11 micrograms kg-1) and IL-1 beta (5 ng kg-1) produced increases in body temperature simultaneously with increases in plasma PGE2 levels. alpha-MSH (5 or 10 micrograms kg-1) attenuated both the increase in body temperature and increases in plasma levels of PGE2. 3. Intracerebroventricular injection of PGE2 (500 ng) produced a monophasic increase in body temperature. alpha-MSH (5 micrograms kg-1) administered 20 min after PGE2 had no effect on the hyperthermic response. 4. alpha-MSH (10 micrograms kg-1) had no effect on either body temperature or plasma levels of PGE2 in response to I.V. injection of sterile saline. 5. These data demonstrate that alpha-MSH inhibits both the pyrogenic actions of LPS, EP, TNF-alpha and IL-1 beta and their ability to increase PGE2 release without affecting the direct actions of PGE2, suggesting the possibility that alpha-MSH may prevent the synthesis of PGE2 either by preventing the actions or release of mediators such as TNF-alpha and IL-1 in response to LPS.
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PMID:Alpha-melanocyte-stimulating hormone suppresses fever and increases in plasma levels of prostaglandin E2 in the rabbit. 140 21

Treatment of an organism with UVB light or PUVA (8-methoxypsoralen + UVA light) not only leads to alterations in the irradiated skin but also to systemic immunomodulation, due to the release of several chemical mediators of immunosuppression like prostaglandins, acute-phase proteins, IL-1 inhibitor, alpha-melanocyte-stimulating hormone, propiomelanocorticotropin or other cytokines. A recently described mediator is urocanic acid, which is transformed by UV light in the skin from the trans- to the cis-isomer and that exerts a systemic immunomodulatory effect. In our experiments, treatment with PUVA or with cis-urocanic acid prevents the rejection of rat heart allografts in 50% and 40% of cases, respectively. Control grafts are rejected in fewer than 10 days. PUVA treatment of donor leukocytes before transfusion into the prospective recipient inhibits only their sensitizing, not their graft-protecting, effect on subsequent skin grafts in mice. PUVA treatment also prevents acute lethal GVH disease in mice after irradiation with a sublethal dose of x-rays and transfusion of semiallogeneic spleen cells. Treatment of recipient mice with cis-urocanic acid has the same effect. The humoral immune response to sheep erythrocytes is not influenced by cis-urocanic acid. These results demonstrate that PUVA treatment or its chemical mediator, cis-urocanic acid, may be used in transplantation and hematology as naturally occurring immunosuppressive agents, especially for the control and manipulation of GVH leukemia reaction.
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PMID:Cis-urocanic acid as a mediator of ultraviolet-light-induced immunosuppression. 159 41

We have demonstrated that centrally administered interleukin-6 (IL-6) stimulates adrenocorticotropin (ACTH) secretion by a direct effect on corticotropin-releasing factor (CRF) release from the hypothalamus. Since metabolites of the arachidonic acid cascade (AAC) have been implicated in mediating actions of cytokines in different tissues and some AAC inhibitors were able to block pyrogenic effects of cytokines and suppress IL-1-induced ACTH secretion, we decided to examine the mechanism of IL-6 action on CRF release in vitro. After a 60-min preincubation in Krebs-Ringer bicarbonate buffer, medial basal hypothalami (MBH) were preincubated for 30 min with dexamethasone (DEX), a phospholipase A2 (PLA2) inhibitor, to block arachidonic acid (AA) formation, or with inhibitors of AA metabolism: a cyclooxygenase inhibitor--indomethacin (IND); a lipoxygenase inhibitor--5,8,11-eicosatriynoic acid (ETI), and an epoxygenase inhibitor--clotrimazole (CLO). Then, the medium was discarded and MBH were incubated with medium or the above compounds and/or IL-6 for 30 min, and CRF release into the incubation medium was measured by radioimmunoassay. As reported previously, 10(-13) M IL-6 increased CRF release, which was significantly suppressed by DEX in a dose-dependent manner. The suppression was already highly significant at a concentration of 10(-11) M DEX and became maximal at 10(-7) M, at which concentration CRF release was no longer stimulated by IL-6. The response to IL-6 was completely blocked at the highest DEX concentration evaluated (10(-5) M). CLO also suppressed IL-6-induced CRF release with a minimal effective dose of 10(-9) M. Suppression was complete at 10(-7) and 10(-5) M.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Involvement of arachidonic acid cascade pathways in interleukin-6-stimulated corticotropin-releasing factor release in vitro. 163 May 86

The effects of intracerebroventricularly (i.c.v.) injected interleukin-1 beta (IL-1 beta: 1, 2.5, 10, and 25 ng) were studied on plasma growth hormone (GH) and prolactin (PRL) concentrations in freely moving rats chronically implanted with i.c.v. cannulas and intracardial catheters. Significant changes in PRL secretion were not found. Small i.c.v. doses of IL-1 stimulated GH secretion 15 min postinjection (significant after 2.5 ng IL-1) whereas high doses of IL-1 suppressed plasma GH concentrations. The stimulation of GH secretion by 2.5 ng IL-1 was abolished when endogenous growth hormone-releasing hormone (GHRH) was immunoneutralized by pretreating the rats with GHRH antibodies. The results indicate that IL-1 elicits GH secretion by stimulating the release of hypothalamic GHRH. The inhibition of GH secretion after high doses of IL-1 is attributed to the previously reported corticotropin-releasing-hormone-releasing activity of IL-1.
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PMID:Stimulation and inhibition of growth hormone secretion by interleukin-1 beta: the involvement of growth hormone-releasing hormone. 164 Oct 70

Intracerebroventricular (ICV) injections of interleukin-1 beta (IL-1 beta) produced a dose-dependent increase in plasma corticosterone and adrenocorticotropic hormone (ACTH) within 2 hr of injection and then declined over the next 24 hr. Using a potent steroidogenic dose of IL-1 beta (5 ng), ICV injection resulted in suppression of splenic macrophage IL-1 secretion following stimulation by LPS in vitro. Macrophage TGF-beta secretion was not affected, indicating a differential action of ICV IL-1 beta on macrophage cytokine production. Following adrenalectomy (ADX), the suppressive effect of ICV IL-1 beta was reversed and resulted in stimulation of macrophage IL-1 secretion, indicating that the suppression was mediated by adrenocorticol activation. However, surgical interruption of the splenic nerve to eliminate autonomic innervation of the spleen also prevented the macrophage suppressive signal in rats given ICV IL-1 beta. Furthermore, the combination of ADX and splenic nerve section resulted in a potent stimulatory effect of ICV IL-1 beta on splenic macrophage IL-1 secretion which was greater than either ADX or splenic nerve section alone. These results support the concept of a negative feedback on macrophage IL-1 secretion by the central action of IL-1 beta and indicate that both the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system mediate this effect.
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PMID:Suppression of splenic macrophage interleukin-1 secretion following intracerebroventricular injection of interleukin-1 beta: evidence for pituitary-adrenal and sympathetic control. 164 53

Opioid peptides appear to be dynamic signaling molecules that are produced within the immune system and are active regulators of an immune response. Furthermore, the receptors for these peptides occurring on immunocyte membranes share characteristics with neuronal opioid receptors, including molecular size, immunogenicity, and the use of specific intracellular signaling pathways. Recent studies of the interaction of opioids with cytokines have indicated that opioid peptides are intimately involved within the immune system. Specifically, opioids, including 2-n-pentyloxy-2-phenyl-4-methyl-morpholine, naloxone, and beta-endorphin, have been shown to interact with IL-2 receptors (134) and regulate production of IL-1 and IL-2 (48-50, 135). Conversely, IL-1 has been shown to up-regulate opioid peptide binding in brain tissue (136). Furthermore, the induction of IL-1 by opioids has also been identified in the invertebrate Mytilus, indicating the evolutionary conservation of this relationship (137). These results seem to typify the intricate association between the immune and neuroendocrine systems through opioid pathways. It is predicted that future endeavors will use this relationship to diagnose and treat specific diseases that have at their basis neuroendocrine and immunologic imbalances.
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PMID:The role of endogenous opioids and their receptors in the immune system. 165 70


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