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)

Effect of different cytokines, human recombinant interleukin-1 alpha and beta (IL-1 alpha, IL-1 beta), interleukin-6 and tumor necrosis factor-alpha (TNF) on adrenocorticotropin (ACTH) secretion was compared in sham-operated rats and those with lesions of the hypothalamic paraventricular nucleus. IL-1 alpha was less active than IL-1 beta in stimulating ACTH in sham-operated rats. Intravenous injection of IL-1 beta in sham-operated animals resulted in a rapid elevation of ACTH secretion. Five days after surgical lesion of the paraventricular nucleus, the main hypothalamic source of hypophysiotropic corticotropin-releasing factor-41, the response to IL-1 beta was attenuated but not abolished. This suggests involvement of extra-paraventricular releasing factors in mediation of ACTH-releasing activity of IL-1 beta, altered responsiveness of pituitary to CRFs, and/or direct action of IL-1 beta on the corticotrope cells. TNF resulted in a biphasic stimulation of ACTH concentration, with peaks at 15 min and 90 min. In paraventricular-lesioned, TNF injected rats both of these ACTH peaks disappeared, suggesting that CRFs from the paraventricular origin mediates ACTH-inducing activity of TNF. IL-6 elevated ACTH secretion much later than the other intravenously injected cytokines, the peak was at 1 h in sham-lesioned rats. Paraventricular lesion completely prevented the increase of ACTH plasma levels after IL-6 injection. These data suggest that: (1) Effect of TNF and IL-6 on hypothalamo-pituitary-adrenal axis is mediated through the hypothalamic paraventricular nucleus and (2) IL-1 beta is able to release ACTH even in the absence of hypothalamic drive.
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PMID:Differential dependence of ACTH secretion induced by various cytokines on the integrity of the paraventricular nucleus. 773 93

The presence of the opioid peptides alpha- and beta-endorphin (-End) but not methionine enkephalin (Met-enk) in in vitro cultures of purified CD4+ T cells, stimulated with concanavalin A in the presence of irradiated spleen cells, resulted in a threefold stimulation of IL-2, IL-4, and IFN-gamma production. The stimulating effect was dependent on the concentration of the peptides and reached optimal values in the dose range from 10(-12) to 10(-10) M. Similar results were obtained when purified CD4+ T cells were stimulated with immobilized anti-CD3, indicating a direct effect of opioid peptides on CD4+ T cells. Moreover, in this system a twofold enhancement of IL-6, but not IL-1, secretion was observed. These stimulatory effects were not mediated through opioid receptors since the peptide fragment beta-End6-31 that lacks the N-terminal opioid receptor binding part was still stimulatory. This is in agreement with our finding that beta-End did not affect cAMP, as described for the triggering of classical opioid receptors. Experiments undertaken to reveal the mechanism of action of opioid peptides suggest an overall enhancement of lymphokine production: (1) enhancement of IL-4 production occurred also in the presence of excess IL-2; and (2) neither IL-1 receptor-antagonizing protein nor anti-IL-6 were capable to abrogate the stimulatory effect on IL-2 and IL-4 production. Finally, the presence and activity of opioid receptors in cultures of CD4+ T cells were substantiated by the fact that the opioid receptor antagonist naloxone by itself enhanced cytokine synthesis, which points to the endogenous production by lymphocytes of down-regulating opioid peptides.
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PMID:Role of opioid peptides in the regulation of cytokine production by murine CD4+ T cells. 790 6

We recently demonstrated that the opioid peptide beta-endorphin (beta-End) has the capacity to stimulate interleukin-2 (IL-2) and IL-4 production by murine CD4+ T cells. Since opioid peptides have been demonstrated to contain stimulatory as well as inhibitory sites, we studied peptide fragments of beta-End to identify a moiety with exclusive stimulatory capacity. To this end, the effects of various opioid peptides on the production of IL-2, IL-4, IL-6, and interferon-gamma (IFN-gamma) by CD4+ T cells were determined. It appeared that two peptide fragments of beta-End, i.e., beta-End6-31 and beta-End18-31, that lack the N-terminal enkephalin part, enhanced IL-2 and IL-4 production to a similar extent as intact beta-End, indicating that the N-terminal part is not involved in the stimulating effects of beta-End. Also the production of IL-6 and IFN-gamma was increased by these peptides. By contrast, the fragments beta-End24-31 and beta-End28-31 did not stimulate the production of the cytokines. Surprisingly, also alpha-End, which is equivalent to beta-End1-16 and hence lacks the sequence comprising amino acids 18 through 31, was stimulatory. This effect was not prevented by naloxone, indicating that opioid receptors were not involved. Moreover, methionine-enkephalin (Met-Enk), which binds to opioid receptors, did not affect cytokine production. Because both alpha-End and beta-End18-31 stimulate cytokine production by CD4+ T cells and do not overlap is sequence, it is concluded that at least two distinct sites of beta-End can exert stimulating effects on cytokine production.
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PMID:Identification of distinct sites of beta-endorphin that stimulate lymphokine production by murine CD4+ T cells. 791 52

Previous studies have demonstrated that stressors alter cellular immune system function, and increase the activity of locus coeruleus neurons. Furthermore, stressors increase the release of corticotropin-releasing hormone (CRH) and locus coeruleus neurons are activated by CRH. Thus, the present study examined whether activation of the locus coeruleus by infusion of CRH modulates the function of blood and spleen lymphocytes assessed in vitro. CRH (100 ng) was administered into the region of the locus coeruleus in awake rats 1 hr before spleen and peripheral blood lymphocytes were collected for culture with nonspecific mitogens. Unilateral or bilateral microinfusion of CRH into the locus coeruleus produced a decrease in blood and spleen T-lymphocyte mitogenic responses to phytohemagglutinin, ConA, and an antibody to the T-lymphocyte antigen receptor. In contrast, infusion of saline into the locus coeruleus or CRH into the surrounding region of the dorsal pons did not alter spleen or blood lymphocyte responses. Plasma concentrations of adrenocorticotropic hormone, corticosterone, and IL-6 were increased by CRH infusion into the locus coeruleus. These results suggest that CRH-evoked activation of the locus coeruleus stimulates the hypophysial adrenal axis, possibly activates the sympathetic nervous system, and results in immunosuppression. Comparable changes in lymphocyte and hormone responses are produced by an aversive stimulus or a conditioned stressor, suggesting that activation of the locus coeruleus may be a component of stressor-induced immune alterations.
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PMID:Locus coeruleus stimulation by corticotropin-releasing hormone suppresses in vitro cellular immune responses. 793 60

The neuropeptides are involved in the immune response and in hormonal homeostasis. In this review, we analyse the interactions between the cytokine, the neuropeptide and the hormonal networks in rheumatoid arthritis (RA). We first consider pituitary-adrenal axis dysfunction in RA. An inappropriate response to cortisol in chronic inflammation has been reported, i.e., a decrease of the corticotropin-releasing-hormone (CRH) secretion by the hypothalamus. In contrast, the immunostimulant hormone prolactin (PRL) is upregulated. PRL is released by the pituitary after stimulation by neuropeptides [serotonin, thyroid-releasing-hormone (TRH), or vasoactive-intestinal-peptide (VIP)], and is down-regulated by pro-inflammatory cytokines (IL-1, IL-6). The decreased testosterone concentration observed in male RA patients is associated with HLA B 15. Thus, an altered sex hormone status and a genetic predisposition are related to HLA antigens, and increase the subject's susceptibility to the development of RA. The terminal C fibres release neurotransmitters such as substance P, neurokinin A and calcitonin-gene-related-peptide (CGRP) within the joints, and contribute to local inflammation, synoviocyte proliferation and collagenase production. The parasympathetic system may attenuate the immune response through the neuropeptide VIP. In contrast, the beta 2 adrenergic fibres of the sympathetic nervous system increase joints degradation in RA. This review presents the currently extensive knowledge regarding the immune-neuro-hormonal network, and its implication in the pathogenesis of RA.
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PMID:Modulation of the immune response by the neuro-endocrine axis in rheumatoid arthritis. 795 11

The present study was designed to investigate the coupling mechanisms linking the immune and the neuroendocrine corticotropic systems in an integrated defense response triggered by an infectious aggression. The experimental paradigm used consisted of the exploration in individual conscious rats of the temporal pattern of increased plasma concentrations of the two stress hormones, adrenocorticotropic hormone (ACTH) and corticosterone (Cort), and of three cytokines known as ACTH stimulators, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and IL-6, after intra-arterial infusions of lipopolysaccharide (LPS) given at three doses, 5 micrograms/kg (LPS-5), 25 micrograms/kg (LPS-25), and 1 mg/kg (LPS-1,000). Blood samples were taken 30 min and immediately before LPS injection (t0) and at 15, 30, 60, 120, 300, and 480 min post-LPS. The three doses of LPS induced ACTH and Cort surges, starting after 30 min for LPS-5 and LPS-25 or 15 min for LPS-1,000 and peaking with a similar amplitude at 60 min before receding slowly to baseline at 480 min for the two lower LPS doses. On the other hand, whatever the LPS dose, none of the three cytokines rose above undetectable basal levels before 60 min. They increased thereafter to culminate 10- to 30-fold above baseline at 60 min (TNF-alpha) or 120 min (IL-1 beta and IL-6) after LPS and declined back to basal levels at 300 min (TNF-alpha, all doses, and IL-6 for LPS-5 and LPS-25). After LPS-25, only IL-1 beta had not regressed to baseline levels at 480 min.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Temporal cascade of plasma level surges in ACTH, corticosterone, and cytokines in endotoxin-challenged rats. 804 20

In the present study we show that the opioid peptide beta-endorphin (beta-End) enhances Ia expression on murine B cells in cultures of unseparated spleen cells, mediated by low concentrations of IL-4 in the absence of antigenic or mitogenic stimulation. Since this effect was not found with purified B cells and no enhancement of IL-4 receptor expression on B cells could be observed, we studied the effect of beta-End on IL-4 production. To this end, purified CD4+ T cells were stimulated with suboptimal concentrations of Con A in the presence of irradiated spleen cells. It was indeed shown that beta-End enhances IL-4 production. To establish the role of macrophages in this process, we measured IL-1 and IL-6 production under the influence of beta-End. Splenic adherent cells as well as peritoneal macrophages produced higher levels of IL-1 and IL-6 in response to beta-End, whereas IL-1 was shown to enhance Ia expression similar to beta-End. Using anti-IL-6 it was demonstrated that IL-6 was required for the stimulation of Ia expression by beta-End. It is concluded that a local increase in beta-End may result in upregulation of Ia expression on B cells, thereby most likely improving their antigen-presenting capacity.
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PMID:Beta-endorphin stimulates Ia expression on mouse B cells by inducing interleukin-4 secretion by CD4+ T cells. 809 50

In addition to the magnocellular hypothalamic nuclei, arginine vasopressin (AVP)-containing neurons have also been identified in limbic structures, including the hippocampus and amygdala. In the present study, we compared the qualitative properties of the in vitro release of AVP from the dissected hypothalamus with the in vitro release from the dissected amygdala and used these release systems to evaluate the interactions with neurotransmitters and cytokines. The areas of the paraventricular nucleus and supraoptic nucleus that contain the AVP neurons and that receive cholinergic innervation are also interleukin (IL)-1 beta immunoreactive. Acetylcholine or high KCl (60 mM) induces AVP release in both regions, and the AVP release is calcium dependent. Acetylcholine-induced AVP release is antagonized by atropine or mecamylamine, indicating that both muscarinic and nicotinic receptors are mediating the cholinergic effect in these brain regions. IL-1 beta (100 U/ml) had no effect on the basal AVP release from the hypothalamus, but significantly potentiated the acetylcholine-induced AVP release, lowering the threshold from 500 to 100 nM. This effect was completely blocked in the presence of neutralizing antibodies to IL-1 beta, atropine (10 microM) or mecamylamine (10 microM). IL-6, like IL-1 beta, also potentiated acetylcholine-induced AVP release, but to a lesser extent. Neither tumor necrosis factor-alpha nor interferon-gamma had any effect on the basal or acetylcholine-induced AVP release from the hypothalamus. None of the cytokines tested had any effect on the basal or acetylcholine-induced AVP release from the amygdala. Our results suggest a hypothalamic site of action of IL-1 beta and IL-6 on the acetylcholine-induced AVP release. The stimulatory effects of IL-1 and IL-6 on adrenocorticotropin release have been ascribed to an increased release of corticotropin-releasing factor (CRF). These data further suggest that, in addition to CRF, AVP plays a role in the bidirectional communication between neuroendoc ine and immune systems. Understanding the mode of interaction between IL-1 beta and IL-6 with AVP could clarify pathophysiologic or toxic effects of high brain levels of these cytokines.
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PMID:IL-1 beta potentiates the acetylcholine-induced release of vasopressin from the hypothalamus in vitro, but not from the amygdala. 815 70

Peripheral administration of endotoxin induces brain-mediated responses, including activation of the hypothalamus-pituitary-adrenal (HPA) axis and changes in thermoregulation. This paper reviews the mechanisms by which endotoxin affects these responses. The effects on thermoregulation are complex and include macrophage-dependent hyperthermic and hypothermic responses. Low doses of endotoxin, given IP, activate peripheral macrophages to produce interleukin (IL)-1 beta, which enters the circulation and acts as a hormonal signal. IL-1 may pass fenestrated endothelium in the median eminence to stimulate corticotropin-releasing hormone (CRH) secretion from the CRH nerve-terminals. In addition, IL-1 may activate brain endothelial cells to produce IL-1, IL-6, prostaglandins, etc., and secrete these substances into the brain. By paracrine actions, these substances may affect neurons (e.g., CRH neurons) or act on microglial cells, which show IL-1-induced IL-1 production and therefore amplify and prolong the intracerebral IL-1 signal. In contrast, high doses of endotoxin given i.v. may directly stimulate endothelial cells to produce IL-1, IL-6, and prostaglandin-E2 (PGE2) and thereby activate the HPA axis in a macrophage-independent manner.
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PMID:Activation of the hypothalamus-pituitary-adrenal axis by bacterial endotoxins: routes and intermediate signals. 819 Aug 40

A panel of long-term murine T lymphocyte clones specific for the glycoprotein of vesicular stomatitis virus (VSV) in association with either H-2I-Ad or I-E(d) was tested for the production of cytokines in both resting and poststimulation states using both in situ hybridization and bioassay. All but one of the clones showed antigen-specific cytolytic activity in a 4-hr 51Cr release assay. Unexpectedly, the clones did not appear to be typical Th1 cells. Five of these T cell clones produced both IL-2 and IFN-gamma but not IL-4 after stimulation with either phorbol 12-myristate 13-acetate (PMA) or concanavalin A (Con A). Some clones constitutively expressed mRNA for IL-2 and INF-gamma. The proliferation of these clones was factor independent, suggesting an autocrine growth mechanism. Three clones produced variable levels of IL-4 mRNA and some, to significant quantities, of IL-2 mRNA. One cytolytic clone produced neither IL-2 nor IL-4 mRNA to detectable levels, although mRNA for IFN-gamma was observed. A noncytolytic, Ag-specific clone produced IL-6, tumor necrosis factor (TNF), and lymphotoxin (LT), but no IL-2, IL-4, or IFN-gamma mRNA. There was a strong quantitative correlation between the expression of IL-2-, INF-gamma-, and LT-specific mRNAs by the clones. All the T cell clones tested which secreted INF-gamma and LT expressed no measurable IL-4 mRNA. We examined expression of several other genes in the panel of clones. These included TNF, met-enkephalin (met-enk), IL-1, and IL-6. IL-1 m-RNA synthesis was not observed in any of the T cell clones. Almost all clones produced TNF mRNA. Parallel bioassays showed that secreted IL-2/IL-4 activity levels and mRNA levels correlated well for all clones. Thus, we observed a great degree of heterogeneity among CD4+ cytolytic T lymphocyte clones.
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PMID:Lymphokine expression profile of resting and stimulated CD4+ CTL clones specific for the glycoprotein of vesicular stomatitis virus. 838 Oct 52


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