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)

Recent evidence has suggested that stress may suppress the immune system and increase the frequency and severity of viral and neoplastic disease. The mechanisms for stress-induced modulation of immune function are unclear, but several neuropeptides are thought to be involved. Because macrophages play an important role in the host defense against infection and neoplasia, several stress-related neuropeptides were screened in efforts to determine whether these substances affect macrophage-mediated tumoricidal activity. Adrenocorticotropin and noradrenaline each completely blocked the capacity of mouse recombinant interferon-gamma (INF-gamma) to activate murine peritoneal macrophages to a tumoricidal state as measured by the lysis of 125I-UdR-labeled melanoma target cells. Vasoactive intestinal peptide significantly potentiated the suppressive effects of noradrenaline. In contrast, neurotensin markedly enhanced the cytolytic capability of peritoneal macrophages activated with INF-gamma. Several other neuropeptides, including substance P, alpha-endorphin, beta-endorphin, Leu-enkephalin, and Met-enkephalin, had no effect on macrophage activation. These findings demonstrate that selected stress-related neuropeptides and neurohormones significantly modulate the capacity of macrophages to attain a tumoricidal state and suggest that alteration of macrophage function by neuropeptides may be a prominent feature of stress-induced enhancement of neoplastic disease.
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PMID:Modulation of macrophage-mediated tumoricidal activity by neuropeptides and neurohormones. 258 37

This study determined the effects of neuropeptides and neuroendocrine hormones at the cellular level of the immune response using a murine macrophage cell line, J774, which exhibits a chemiluminescent oxidative burst upon acute stimulation with zymosan. We report that the zymosan-triggered oxidative burst of J774 cells can be modulated by the opioid peptides beta-endorphin (beta-END) and dynorphin A (DYN) in a naloxone-reversible fashion. Norepinephrine (NE) also modulated chemiluminescence (CL) emission of J774 cells, with dose-dependent suppression of CL dependent upon co-incubation with gamma-interferon (gamma-INF). Without gamma-INF co-incubation, NE shared with the opioid peptides beta-END and DYN the ability to modulate oxidative burst, producing an inverted-U dose response. These data indicate that J774 cells may be useful for explaining some mechanisms through which the neuroendocrine system interacts with the immune system.
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PMID:Modulation of chemiluminescence in a murine macrophage cell line by neuroendocrine hormones. 810 66

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

The successful therapeutic use of interferon-alpha (IFN-alpha) in myeloproliferative disorders offered the possibility to test its acute and long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis in humans. ACTH and cortisol plasma concentrations were measured in 8 patients hourly starting from 4 p.m. through 12 p.m. on three occasions. The first time all patients were studied before initiation of therapy, when the vehicle was injected alone. The patients were studied again on day 1 of IFN-alpha therapy (5 million units) and once more after 3 weeks of therapy. On the control day, plasma concentrations of ACTH and cortisol were in the range expected for this time of day. In contrast, after the first administration of IFN-alpha a significant stimulation of the HPA axis was observed. After 3 weeks of IFN-alpha therapy, no significant stimulation of the HPA axis occurred after administration of IFN-alpha. IFN-alpha-induced adaptive changes in the HPA axis were also indicated by a significantly enhanced ACTH and cortisol response to exogenously administered supramaximal doses of corticotropin-releasing hormone (CRH) when the patients had been on IFN-alpha treatment for 3 weeks. To determine the exact locus of the IFN-alpha action, in vitro experiments were performed using rat hypothalamic organ and primary pituitary and adrenal cell culture systems. Thereby a significant stimulation of hypothalamic CRH secretion and rat adrenal corticosterone production was observed after INF-alpha at concentrations of 5 x 10(-8) M or 10(-7) M respectively. In contrast, no direct IFN-alpha effect on pituitary ACTH secretion could be observed in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interferon-alpha stimulates the hypothalamic-pituitary-adrenal axis in vivo and in vitro. 839 62

alpha-Melanocyte-stimulating hormone (alpha-MSH), a tridecapeptide derived from pro-opiomelanocortin, has potent antiinflammatory activity in laboratory animals. alpha-MSH inhibits nitric oxide production by murine macrophages, an influence believed to reflect activation of an autocrine circuit in these cells, one that is based on production and release of alpha-MSH and subsequent stimulation of melanocortin receptors. We found that THP-1 cells, human monocytic cells, produced alpha-MSH; this production was increased by interleukin-6, tumor necrosis factor a, or concanavalin A. These cells also expressed the gene for the human alpha-MSH receptor MC1. Unlike murine macrophages, THP-1 cells produced little nitrite in response to interferon-gamma (IFN-gamma) and lipopolysaccharide, and a-MSH inhibited this production only slightly. However, production of neopterin, a presumed primate homologue of nitric oxide in lower animals, was increased in THP-1 cells stimulated with INF-gamma plus TNF-alpha and alpha-MSH significantly inhibited this production. The evidence indicates that an autocrine regulatory circuit based on alpha-MSH occurs in human monocyte/macrophages much as in murine macrophages. alpha-MSH-induced modulation of specific inflammatory mediators/cytotoxic agents appears to differ depending on the importance of the mediators in the myelomonocytic cells of different species.
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PMID:alpha-MSH production, receptors, and influence on neopterin in a human monocyte/macrophage cell line. 860 97

Several cytokines, which are the major mediators of the inflammatory responses, are well-known to stimulate the hypothalamopituitary corticotropin-releasing hormone (CRH)/adrenocorticotropic hormone (ACTH) system, thereby evoking secretory responses by the adrenal cortex. Many of these cytokines, including interleukin-1 (IL-1), IL-2, IL-6, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (INF-gamma) are synthesized in the adrenal gland by both parenchymal cells and resident macrophages, and the release of some of them (e.g., IL-6 and TNF-alpha) is regulated by the main agonists of steroid hormone secretion (e.g., ACTH and angiotensin-II) and bacterial endotoxins. Adrenocortical and adrenomedullary cells are provided with specific receptors for IL-1, IL-2, and IL-6. IL-1 and TNF-alpha directly inhibit aldosterone secretion of zona glomerulosa cells, whereas IL-6 enhances it. IL-2, IL-3, IL-6, and INF-alpha are able to directly stimulate glucocorticoid production by zona fasciculata and zona reticularis cells, whereas IL-1 exerts an analogous effect through an indirect mechanism involving the stimulation of catecholamine release by chromaffin cells and/or the activation of the intramedullary CRH/ACTH system; again, TNF-alpha depresses glucocorticoid synthesis. IL-6 raises androgen secretion by inner adrenocortical layers. IL-1 enhances the proliferation of adrenocortical cells, and findings suggest that cytokines may control the apoptotic deletion of senescent zona reticularis cells. The relevance of the intraadrenal cytokine system in the fine-tuning of the secretion and growth of the adrenal cortex under normal conditions remains to be explored. However, indirect proof is available that local immune-endocrine interactions may play an important role in modulating adrenal responses to inflammatory and immune challenges and stresses.
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PMID:Immune-endocrine interactions in the mammalian adrenal gland: facts and hypotheses. 966 67

The responses of plasma cortisol and adrenocorticotropic hormone (ACTH) were examined to intravenous injection of recombinant bovine tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (INF-gamma) in Holstein cows. INF-gamma induced dose-dependent rises in the plasma levels of both cortisol and ACTH, while TNF-alpha induced comparable plasma cortisol responses with much smaller rises in plasma ACTH. The results suggest a direct stimulatory action of TNF-alpha on cortisol secretion from the adrenal gland in cattle.
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PMID:Adrenocortical responses to tumor necrosis factor-alpha and interferon-gamma in cattle. 1548 63

Associations between stress and health outcomes have now been carefully documented, but the mechanisms by which stress specifically influences disease susceptibility and outcome remain poorly understood. Recent evidence indicates that glucocorticoids (GCs) and catecholamines (CAs), the major stress hormones, inhibit systemically IL-12, TNF-alpha, and INF-gamma, but upregulate IL-10, IL-4, and TGF-beta production. Thus, during an immune and inflammatory response, the activation of the stress system, through induction of a Th2 shift may protect the organism from systemic "overshooting" with T helper lymphocyte 1 (Th1)/proinflammatory cytokines. In certain local responses and under certain conditions, however, stress hormones may actually facilitate inflammation, through induction of IL-1, IL-6, IL-8, IL-18, TNF-alpha, and CRP production, and through activation of the corticotropin-releasing hormone (CRH)/substance P(SP)-histamine axis. Autoimmunity, chronic infections, major depression, and atherosclerosis are characterized by a dysregulation of the pro/anti-inflammatory and Th1/Th2 cytokine balance. Thus, hyperactive or hypoactive stress system, and a dysfunctional neuroendocrine-immune interface associated with abnormalities of the "systemic anti-inflammatory feedback" and/or "hyperactivity" of the local proinflammatory factors may contribute to the pathogenesis of these diseases. Conditions that are associated with significant changes in stress system activity, such as acute or chronic stress, cessation of chronic stress, pregnancy and the postpartum period, or rheumatoid arthritis (RA) through modulation of the systemic or local pro/anti-inflammatory and Th1/Th2 cytokine balance, may suppress or potentiate disease activity and/or progression. Thus, stress hormones-induced inhibition or upregulation of innate and Th cytokine production may represent an important mechanism by which stress affects disease susceptibility, activity, and outcome of various immune-related diseases.
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PMID:Stress system activity, innate and T helper cytokines, and susceptibility to immune-related diseases. 1685 35