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 assess cell-mediated immunity in depression and anxiety disorders and to elucidate whether immunodysfunction might be related to a high opioid activity, a prospective study of patients with major depression (n = 34) or anxiety disorders (n = 21) was performed. Cellular immunity tests, the in vitro effects of naloxone on monocytes, and beta-endorphin plasma levels were investigated. Peripheral blood mononuclear cells and some monocyte parameters were determined by flow cytometry. Natural killer (NK) cell activity was studied by cytotoxicity, gamma-interferon production by a standard bioassay, monocytic phagocytosis by ingestion of Candida albicans and latex, and blastogenesis by stimulation with phytohaemaglutinin. In major depression and anxiety: 1) a marked reduction in the number of monocytes that ingested particles and expressed cytoskeletal intermediate filaments and surface structures (CR1 receptors and HLA-DR antigens); 2) a monocytosis that was not able to normalize the count of functioning monocytes; 3) an in vitro correction of the monocyte dysfunction by naloxone; 4) a decrease in NK cell number and activity; and 6) an anergy to candidin and tuberculin and a diminished lectin-induced blastogenesis were observed. Some of these immune changes correlated closely with plasma beta-endorphin abnormally high in all the cases. In conclusion, a naloxone-reversible monocyte dysfunction, associated to decreased NK activity and cell-mediated hypersensitivity, was found together with high of beta-endorphin plasma levels. In addition, results suggest that these immunological alterations may be useful in the clinical management of patients with these psychiatric diseases.
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PMID:Opioid peptides and immunodysfunction in patients with major depression and anxiety disorders. 1022 12

The effects of interferons (IFNs) IFN-alpha, IFN-beta and IFN-gamma on the production of cortisol in bovine adrenal fasciculata cells have been investigated. Pretreatment of the fasciculata cells with recombinant interferon-alpha-2b from man (over 300 units mL(-1)), but not with fibroblast IFN-beta or recombinant IFN-gamma from man, reduced the production of cortisol in cells stimulated with adrenocorticotropin (ACTH) (1 nM). IFN-alpha-2b inhibited ACTH-induced cortisol production in a concentration- (300-15000 units mL(-1)) and time- (2-24h) dependent manner. The inhibitory effect of IFN-alpha-2b on the production was abolished when the cells were simultaneously treated with anti-IFN-alpha antibody, and it was reversible. IFN-alpha-2b also inhibited dibutyryl cyclic AMP-induced production of cortisol but not pregnenolone-induced production. The effect of IFN-alpha-2b was not influenced by increases in external ACTH and Ca2+ concentrations and IFN-alpha-2b did not affect the ACTH-induced increase in cyclic AMP level in the cells. These results strongly suggest that IFN-alpha-2b reduces ACTH-induced production of cortisol in bovine adrenal fasciculata cells by affecting the early process of cortisol synthesis. The results also indicate that IFNs might not directly affect steroidogenesis in the adrenal cortex in-vivo, because of the requirement of high concentrations of IFN-alpha-2b for inhibition, and because of the ineffectiveness of IFN-beta and IFN-gamma.
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PMID:Effects of interferons on cortisol production in bovine adrenal fasciculata cells stimulated by adrenocorticotropin. 1038 20

Alpha-melanocyte stimulating hormone (alpha-MSH) was originally documented as a peptide that induced pigmentation in skin. However, more recent work suggests that it acts as a potent anti-inflammatory molecule in several tissues including nerve. Alpha-MSH works by directly inhibiting cytokines that cause inflammation, in particular tumour necrosis factor-alpha, interleukin-1beta, interleukin-6 and gamma-interferon. A common mechanism of inhibition is via the NF-kappaB transcription factor. We investigated the ability of alpha-MSH to inhibit the activation of NF-kappaB in cultured rat primary olfactory ensheathing cells stimulated with tumour necrosis factor-alpha or gamma-interferon. Both cytokines activated NF-kappaB rapidly (after 60 min incubation), observed as a translocation from cytoplasm to nucleus. alpha-MSH inhibited this activation (and hence nuclear translocation) by approximately 50% for both cytokines. The anti-inflammatory properties of this peptide in neural cells may therefore support a basis for treating CNS injury, where inflammation is a major problem.
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PMID:Alpha-MSH inhibits inflammatory signalling in olfactory ensheathing cells. 1462 42

The role of cytokines in depression was first considered when the cytokine interferon resulted in "sickness behaviour", the symptoms of which are similar to those of major depression. The latter is associated with an increase in pro-inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha). These cytokines are potent modulators of corticotropin-releasing hormone (CRH) which produces heightened hypothalamic-pituitary-adrenal axis (HPA) activity characterized by increases in ACTH and cortisol, both of which are reported elevated in major depression. Antidepressant treatment has immunomodulatory effects with increases in the production of IL-10, which is an anti-inflammatory cytokine. This review based on a Medline search from 1980-2003, focuses on the evidence available of cytokine changes in acute stress, chronic stress and major depression. It examines the effects of antidepressant treatment on immune parameters in both animal models and clinical trials. We suggest that future antidepressants may target the immune system by either blocking the actions of pro-inflammatory cytokines or increasing the production of anti-inflammatory cytokines.
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PMID:Cytokines: abnormalities in major depression and implications for pharmacological treatment. 1530 43

We report that mice with a targeted null mutation in the interferon type I receptor (IFN-RI), which cannot respond to such IFNs as IFNalpha and IFNbeta, have a 30% reduction in time spent in spontaneous rapid eye movement sleep (REMS) as a consequence of a reduced number of REMS episodes. Time spent in nonrapid eye movement sleep (NREMS) was essentially unaltered in IFN-RI knockouts (KOs) compared to 129 SvEv controls. Body temperature and locomotor activity were similar in both strains of mice. Hypothalamic expression of mRNAs for molecules previously linked to sleep-wake regulation and an IFN-inducible antiviral gene, 2',5'-oligoadenylate synthetase 1a (OAS), were determined by real-time reverse-transcriptase polymerase chain reaction (RT2-PCR). The level of hypocretin A mRNA was elevated in IFN-RI KO mice compared to 129 SvEv mice, while prolactin mRNA and OAS mRNA levels were suppressed. Vasoactive intestinal peptide (VIP) and corticotropin-releasing hormone (CRH) mRNA levels were unchanged relative to controls. Serum prolactin levels were similar in both strains. Results are consistent with the hypothesis that increased hypocretin and reduced prolactin in the hypothalamus of IFN-RI KO mice are responsible for their reduced REMS. In addition, the reduced OAS expression may result in modulation of prolactin receptor signaling and thus contribute to suppression of REMS.
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PMID:Mice deficient in the interferon type I receptor have reduced REM sleep and altered hypothalamic hypocretin, prolactin and 2',5'-oligoadenylate synthetase expression. 1549 63

Various skin disorders may occur during antiviral therapy with interferon (IFN) and ribavirin (RBV) for chronic hepatitis C. This article describes to our knowledge the first report of lingual hyperpigmentation during pegylated (PEG)-IFN/RBV combination therapy in five dark-skinned hepatitis C virus (HCV) patients. Lingual pigmentation during antiviral therapy was not associated with age, gender, HCV genotype, doses of RBV, or duration of the treatment or treatment outcome. Since IFN increases the expression of alpha-melanocyte-stimulating hormone (MSH) surface receptors, the use of PEG-IFN having a longer plasma half-life may even increase incidence for such cutaneous side effects particularly in dark-skinned HCV patients.
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PMID:Tongue and skin hyperpigmentation during PEG-interferon-alpha/ribavirin therapy in dark-skinned non-Caucasian patients with chronic hepatitis C. 1640 55

The goal of this review is to highlight the wide range of biological activities displayed by purines, with particular emphasis on new purine-based agents which find potential application as chemical-biology tools and/or therapeutic agents. The expanding interest in the biological properties of polyfunctionalized purine derivatives issues, in large part, from the development of rapid high-throughput screening essays for new protein targets, and the corresponding development of efficient synthetic methodology adapted to the construction of highly diverse purine libraries. Purine-based compounds have found new applications as inducers of interferon and lineage-committed cell dedifferentiation, agonists and antagonists of adenosine receptors, ligands of corticotropin-releasing hormone receptors, and as inhibitors of HSP90, Src kinase, p38alpha MAP kinase, sulfotransferases, phosphodiesterases, and Cdks. The scope of application of purines in biology is most certainly far from being exhausted. Testing purine derivatives against the multitude of biological targets for which small molecule probes have not yet been found should thus be a natural reflex.
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PMID:The purines: potent and versatile small molecule inhibitors and modulators of key biological targets. 1650 44

Multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system, is the most common crippling neurological disease of young adults in the US. The 2 basic clinical forms of the disease (relapsing and progressive), which can occur singly or in combination, encompass a wide range of clinical severities are usually established between 18 and 35 years of age and can persist an entire lifetime. Life expectancy of 20 years is 85% of normal. Historically, the standard proven and generally accepted clinical treatment of the disease has been corticotropin (ACTH) and methylprednisolone, which benefited clinical relapses but had no effect on clinical disability (the most important factor influencing the lives of individual MS patients) or other aspects of the chronic course of the disease. The most important new development in the treatment of MS has been the introduction of interferon beta into the clinic. Two forms of recombinant interferon beta have been approved by the FDA for use in relapsing MS: interferon beta-1b (IFN-beta-1b) and interferon beta-1a (IFN-beta-1a). The efficacy of IFN-beta-1b in the treatment of relapsing-remitting MS was established first but no effect on physical disability progression was discerned. In contrast, well designed trials of intramuscular IFN-beta-1a (Avonex((R))) 6.0 MIU (30micro) weekly and subcutaneous IFN-alpha-1a (Rebif((R))) 6 MIU (22microg) or 12 MIU (44microg) 3 times weekly produced a significant delay in the time to sustained progression in physical disability, the first MS treatment to exert such a prophylactic effect. Additionally, IFN-beta-1a significantly reduced clinical relapses and acute and chronic brain lesions revealed by MRI examinations. It is currently believed that IFN-beta-1a treatment alters the fundamental course of relapsing MS. The mechanisms of the therapeutic benefit of recombinant interferon betas are incompletely understood but may include augmentation of suppressor T cell function, inhibition of interferon gamma actions, inhibition of T cell activation, or induction of interleukin-10 gene transcription.
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PMID:Appropriate use of interferon beta-1a in multiple sclerosis. 1803 Nov 26

The birth process induces fetal stress. Stress has profound effects on the immune system, also by acting on the trafficking of leukocytes, a process in which adhesion and chemotaxis are primordial and critical events for the development of effective antimicrobial defenses. The newborn is rapidly challenged by a microflora at the epithelia linings and therefore depending on early, innate immunity onset. The objective of the study was to investigate the immune response in cord blood from newborns in relation to different degrees of fetal stress, with focus on neutrophil chemotaxis. We analyzed in vitro transmigration ability of neutrophils and their CD11b expression, measured total white blood count (WBC) and the major leukocyte populations, interleukin (IL)-8, interferon (IFN)-gamma, and soluble E-Selectin, as well as relevant immuno-modulating hormones in infants born at term after Cesarean section prior to the start of labor (n = 55), normal vaginal delivery (n = 87), and assisted delivery (n = 26). Arterial pH and lactate were used as stress markers. We found that spontaneous and IL-8-induced transmigration ability of neutrophils from newborns after normal delivery was significantly higher compared with that of neutrophils from Cesarean section or from adults. With a progressive increase in fetal stress, there were significant elevations in total WBC, in particular neutrophils and monocytes, as well as an enhanced IL-8 and soluble E-Selectin level. Assisted delivery, associated with the highest degree of fetal stress in addition had an enhanced lymphocyte and monocytes count as well as an increased IFN-gamma level. There were significant direct correlations between neutrophils and monocytes, respectively, with cortisol, beta-endorphin, and prolactin. Interferon-gamma was directly related to dopamine, as well as to the lymphocyte and monocyte count. The setting of the HPA-axis at birth is a promoter of an alarm response and a surge of neuroendocrine immuno-modulating factors that enhances antimicrobial defenses of the newborn. We speculate that IL-8 induced by normal labor may be a priming factor for an increased neutrophil chemotaxis through the pre-activated endothelium of the fetus. Assisted delivery may trigger excessive recruitment of additional inflammatory cells and IFN-gamma release.
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PMID:The stress of birth enhances in vitro spontaneous and IL-8-induced neutrophil chemotaxis in the human newborn. 1807 18

Endogenous opioids participate in growth regulation. Liver regeneration relates to growth. Thus, we explored the expression of methionine enkephalin and of the delta opioid receptor 1 immunoreactivities with a polyclonal rabbit antibody in deparaffinized liver of patients with chronic liver disease. Fifteen of a total of fifty-eight samples expressed both opioid receptor and methionine enkephalin immunoreactivities, one sample expressed receptor but not methionine enkephalin immunoreactivity, and two samples expressed methionine enkephalin but not receptor immunoreactivity. Ten of the 45 (22%) samples from patients with chronic hepatitis C, four of the eight (50%) samples from patients with chronic hepatitis B, one of the five (20%) samples from patients with autoimmune hepatitis expressed both met-enkephalin and delta opioid receptor 1 immunoreactivities. The expression of methionine enkephalin and delta opioid receptor 1 immunoreactivities suggests that methionine enkephalin exerts an effect in situ, which may include regulation of liver regeneration. However, another possibility that concerns an effect of methionine enkephalin in the liver arises. As morphine, which acts via opioid receptors, has been reported to increase hepatitis C virus replication in vitro and to interfere with the antiviral effect of interferon, methionine enkephalin, analogous to morphine, may enhance the replication of the hepatitis C virus in the liver of patients with this type of viral hepatitis, and interfere with the therapeutic effect of interferon. These results may explain at least in part, why some patients with chronic hepatitis C infection do not respond to interferon therapy.
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PMID:Human hepatic met-enkephalin and delta opioid receptor-1 immunoreactivities in viral and autoimmune hepatitis. 1875 88


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