Peripheral blood mononuclear cell beta-endorphin concentration is decreased in chronic fatigue syndrome and fibromyalgia but not in depression: preliminary report
Female; Humans; Male; Adult; Sensitivity and Specificity; Reproducibility of Results; Biomarkers of Pain; Diagnosis; Differential; Leukocytes; Mononuclear/immunology/metabolism; Fatigue Syndrome; beta-Endorphin/blood/immunology/metabolism; Chronic/blood/diagnosis/immunology; Depression/blood/diagnosis; Fibromyalgia/blood/diagnosis/immunology
OBJECTIVE: The aim of this study was to examine the possible role of the immune system in the pathophysiology of chronic fatigue syndrome and fibromyalgia syndrome and in the differential diagnosis of depression by investigating changes in peripheral blood mononuclear cell levels of beta-endorphin, an endogenous opioid known to be involved in regulation of the immune system function. DESIGN: Beta-endorphin concentrations were measured by radioimmunoassay in peripheral blood mononuclear cells from healthy controls (n = 8) and patients with chronic fatigue syndrome (n = 17), fibromyalgia syndrome (n = 5), or depression (n = 10). RESULTS: Beta-endorphin concentrations were significantly lower in patients with chronic fatigue syndrome or fibromyalgia syndrome than in normal subjects and depressed patients (p <0.001 and p <0.01, respectively). They were significantly higher in depressed patients than in controls (p <0.01). CONCLUSIONS: Evaluation of peripheral blood mononuclear cell beta-endorphin concentrations could represent a diagnostic tool for chronic fatigue syndrome and fibromyalgia and help with differential diagnosis of these syndromes versus depression. The results obtained are also consistent with the hypothesis that the immune system is activated in both chronic fatigue syndrome and fibromyalgia syndrome.
2002
Panerai AE; Vecchiet J; Panzeri P; Meroni P; Scarone S; Pizzigallo E; Giamberardino MA; Sacerdote P
The Clinical Journal Of Pain
2002
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Journal Article
<a href="http://doi.org/10.1097/00002508-200207000-00008" target="_blank" rel="noreferrer">10.1097/00002508-200207000-00008</a>
Beta endorphin concentrations in PBMC of patients with different clinical phenotypes of multiple sclerosis
Female; Humans; Male; Adult; Middle Aged; Magnetic Resonance Imaging; Phenotype; Biomarkers of Pain; Brain/pathology; Leukocytes; Mononuclear/chemistry; beta-Endorphin/blood/genetics; Multiple Sclerosis/blood/genetics/pathology
The possible link between the opioid peptide beta endorphin and the heterogeneity of the clinical course of multiple sclerosis (MS) was investigated. Peripheral blood mononuclear cells (PBMC) concentrations of beta endorphin were measured in 50 patients in different phases of MS. Thirty nine patients also underwent post-contrast magnetic resonance imaging of the brain. Among MS forms, the highest beta endorphin concentrations were found in PBMC from patients with relapsing remitting MS and the lowest in patients with the progressive forms. Average beta endorphin concentrations were lower, although not significantly, in patients with than in those without magnetic resonance imaging enhanced lesions. These data suggest that beta endorphin may have a role in the downregulation of the inflammatory process.
2003
Gironi M; Furlan R; Rovaris M; Comi G; Filippi M; Panerai AE; Sacerdote P
Journal Of Neurology, Neurosurgery, And Psychiatry
2003
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Journal Article
<a href="http://doi.org/10.1136/jnnp.74.4.495" target="_blank" rel="noreferrer">10.1136/jnnp.74.4.495</a>
Intermittent but not continuous inescapable footshock stress affects immune responses and immunocyte beta-endorphin concentrations in the rat
Male; Time Factors; Animals; Acute Disease; Rats; Comparative Study; Receptors; beta-Endorphin/analysis; Corticosterone/blood; Corticotropin-Releasing Hormone/antagonists & inhibitors; Corticotropin-Releasing Hormone/blood/pharmacology/physiology; Electroshock/adverse effects; Foot; Helplessness; Killer Cells; Learned; Lymphocyte Activation; Lymphoid Tissue/chemistry; Natural/immunology; Neuroimmunomodulation/physiology; Peptide Fragments/pharmacology; Spleen/immunology; Sprague-Dawley; Stress/etiology/immunology
It is well known that a variety of stressors influence immune responses. The opioid peptide-beta-endorphin (BE) is deeply involved in stress responses, is synthesized in cells of the immune system, and participates in the modulation of immune function. We analyzed the ability of two different stress paradigms to modulate the beta-endorphin concentrations in the immune cells and the immune response in the rat. Two and 24 h after the exposure to inescapable intermittent footshock (1.6 mA, 60 Hz, 1 s, every 5 s for 20 min) the concentrations of beta-endorphin in splenocytes, peripheral blood mononuclear cells and lymph node cells were significantly increased. In contrast, the exposure to a continuous footshock for 3 min did not affect the concentrations of the opioid peptide. Similarly, phytohemoagglutinin-induced proliferation of splenocytes and natural killer activity were significantly impaired only after the exposure to intermittent footshock stress. On the contrary, plasma corticosterone levels were similarly elevated after both paradigms of stress. The pretreatment with the corticotropin-releasing hormone (CRH) receptor antagonist prevented both the stress-induced increase of immunocyte BE and immunosuppression. In conclusion, our data suggest that intermittent and continuous footshock stressors activate different neuroendocrine responses and that CRH plays a central role in mediating the immune effects of the intermittent footshock stress. The possible relationship between the beta-endorphin changes and immunosuppression is discussed.
1994
Sacerdote P; Manfredi B; Bianchi M; Panerai AE
Brain, Behavior, And Immunity
1994
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Journal Article
<a href="http://doi.org/10.1006/brbi.1994.1023" target="_blank" rel="noreferrer">10.1006/brbi.1994.1023</a>
T-lymphocyte cholecystokinin-8 and beta-endorphin concentrations in eating disorders: I. Anorexia nervosa
Child; Female; Humans; Adult; Treatment Outcome; Combined Modality Therapy; adolescent; Comparative Study; beta-Endorphin/blood; Cognitive Therapy; Anorexia Nervosa/blood/therapy; Antidepressive Agents/administration & dosage; Dibenzocycloheptenes/administration & dosage; Fluoxetine/administration & dosage; Nortriptyline/administration & dosage; Sincalide/blood; T-Lymphocytes/drug effects/metabolism
Baseline concentrations of cholecystokinin-8 (CCK-8) and beta-endorphin (beta-EP) were measured in T-lymphocytes from 33 restricting patients with anorexia nervosa (AN-R), 23 binging/purging patients with anorexia nervosa (AN-BP), and 24 healthy volunteers. CCK-8 basal values were significantly lower and beta-EP values significantly higher in AN-R and AN-BP patients than in normal volunteers. Levels of the peptides were measured three more times during a 4-month combined cognitive-behavioral/psychopharmacological treatment (nortriptyline or fluoxetine in AN-R, fluoxetine or amineptine in AN-BP). CCK-8 values fluctuated (nonsignificantly) during each treatment, while beta-EP values decreased (to a significant degree only in fluoxetine-treated AN-R patients).
1995
Brambilla F; Brunetta M; Peirone A; Perna G; Sacerdote P; Manfredi B; Panerai AE
Psychiatry Research
1995
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Journal Article
<a href="http://doi.org/10.1016/0165-1781(95)02664-9" target="_blank" rel="noreferrer">10.1016/0165-1781(95)02664-9</a>
T-lymphocyte concentrations of cholecystokinin-8 and beta-endorphin in eating disorders: II. Bulimia nervosa
Female; Humans; Adult; Middle Aged; Treatment Outcome; Antidepressive Agents; Combined Modality Therapy; adolescent; Comparative Study; beta-Endorphin/blood; Cognitive Therapy; Dibenzocycloheptenes/administration & dosage; Sincalide/blood; T-Lymphocytes/drug effects/metabolism; Bulimia/blood/therapy; Fluvoxamine/administration & dosage; Serotonin Uptake Inhibitors/administration & dosage; Tricyclic/administration & dosage
Concentrations of cholecystokinin-8 (CCK-8) and beta-endorphin (beta-EP) in T-lymphocytes of 26 women with bulimia nervosa (BN) and in 26 age- and sex-matched healthy comparison subjects were measured. Ten patients were then treated with 300 mg/day of fluvoxamine, p.o., and five patients were treated with 300 mg/day of amineptine, p.o., for 4 months. Concentrations of the two peptides were measured again after 1, 2, and 4 months of therapy. Basal CCK-8 values were significantly lower in patients than in healthy subjects. During fluvoxamine therapy, CCK-8 values increased, reaching normal levels by month 4 of treatment. No such increase occurred during amineptine therapy. Baseline beta-EP values were normal in the bulimic patients but had declined by month 4 of fluvoxamine therapy.
1995
Brambilla F; Brunetta M; Draisci A; Peirone A; Perna G; Sacerdote P; Manfredi B; Panerai AE
Psychiatry Research
1995
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Journal Article
<a href="http://doi.org/10.1016/0165-1781(95)02674-6" target="_blank" rel="noreferrer">10.1016/0165-1781(95)02674-6</a>
Age-related changes of beta-endorphin and cholecystokinin in human and rat mononuclear cells
Humans; Male; Adult; Aged; Middle Aged; Animals; Rats; 80 and over; beta-Endorphin/blood; Lymphocyte Activation; Aging/blood/immunology; Cholecystokinin/blood; In Vitro; Interleukin-2/biosynthesis; Leukocytes; Mononuclear/immunology/metabolism
Beta-endorphin (BE) and cholecystokinin (CCK) were measured in fresh PBMC isolated from human subjects and rats. The BE and CCK PBMC contents increased significantly with age both in human and rat models. Moreover, polyclonal stimulation induced a significant decrease of BE but not CCK contents in mononuclear cells from human aged subjects. The time course of changes in BE and CCK concentrations observed in fresh and cultured cells from subjects of different ages did not directly correlate to the time course of age-associated impairment of lectin-induced lymphocyte proliferative response and interleukin-2 synthesis. In fact, the lymphocyte functional defects were significantly observed only in the 71-99 year age group, whereas the neuropeptide changes were already evident in the 31-50 age group. Since BE has been shown to participate in the modulation of the immune system, the age-related modifications of PBMC BE could play a role in the immunodepression observed during aging.
1991
Sacerdote P; Breda M; Barcellini W; Meroni PL; Panerai AE
Peptides
1991
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Journal Article
<a href="http://doi.org/10.1016/0196-9781(91)90219-f" target="_blank" rel="noreferrer">10.1016/0196-9781(91)90219-f</a>
Age-related changes in mitogen-induced beta-endorphin release from human peripheral blood mononuclear cells
Humans; Adult; Middle Aged; Biomarkers of Pain; Leukocytes; Aging/blood; beta-Endorphin/metabolism; Calcium-Transporting ATPases/antagonists & inhibitors; Calcium/blood; Concanavalin A/pharmacology; Homeostasis/drug effects; Ionomycin/pharmacology; Mitogens/pharmacology; Mononuclear/cytology/drug effects; Phytohemagglutinins/pharmacology; Terpenes/pharmacology; Thapsigargin
beta-Endorphin is an opioid peptide synthesized in the pituitary, hypothalamus, and immunocytes, known to affect immune responses both when added in vitro and when its synthesis is increased in vivo (e.g., during stress). We show here that, similar to its concentrations in peripheral blood mononuclear cells, the release of the opioid peptide from these cells after stimulation with polyclonal mitogens such as PHA or Con-A is also age dependent. Moreover, the effect of both mitogens on Ca2+ homeostasis changes with age. Finally, the ionophore ionomycin and the Ca2+ ATPase blocker thapsigargin induce the same age related effect on beta-endorphin release. For these reasons, we suggest that calcium homeostasis might be important for the differences observed in the release of the opioid from cells obtained from younger ( or = 45 years) volunteers.
1995
Manfredi B; Clementi E; Sacerdote P; Bassetti M; Panerai AE
Peptides
1995
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Journal Article
<a href="http://doi.org/10.1016/0196-9781(95)00030-n" target="_blank" rel="noreferrer">10.1016/0196-9781(95)00030-n</a>
Brain and gut neuropeptides in peripheral blood mononuclear cells
Humans; Male; Adult; Aged; Middle Aged; Brain; Animals; Rats; 80 and over; Sprague-Dawley; Aging/metabolism; beta-Endorphin/blood/pharmacology; Chemotaxis/drug effects; Cholecystokinin/blood/pharmacology; Digestive System; Headache/blood; Lymphocytes/metabolism; Neuropeptides/blood; Schizophrenia/blood; Vasoactive Intestinal Peptide/blood/pharmacology
Neuropeptides, initially thought to be common features of gut and brain, are only synthesized in immune cells and modulate immune functions. The presence and possible functions of these peptides in immune cells in both physiological or pathological conditions have been investigated in our laboratory in the last years. Some of the data obtained are reviewed here, and future developments of the field are indicated.
1993
Panerai AE; Sacerdote P
Journal Of Physiology, Paris
1993
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Journal Article
<a href="http://doi.org/10.1016/0928-4257(93)90034-q" target="_blank" rel="noreferrer">10.1016/0928-4257(93)90034-q</a>
Beta-endorphin levels in peripheral blood mononuclear cells and long-term naltrexone treatment in autistic children
Child; Humans; Preschool; Biomarkers of Pain; Leukocytes; beta-Endorphin/metabolism; Autistic Disorder/drug therapy/metabolism; Cognition/drug effects; Mononuclear/drug effects/metabolism; Naltrexone/pharmacology/therapeutic use; Narcotic Antagonists/pharmacology/therapeutic use; Stereotyped Behavior/drug effects
We assessed the clinical and biological effects of high-dose, long-term Naltrexone (NTX) treatment in 11 children (3-11 years), who had been diagnosed as autistic. The drug was given following an open design, for 12 weeks. Beta-Endorphin (beta-END) was assayed in peripheral blood mononuclear cells after 1 and 3 months of treatment, and 6 months after the completion of the course. Baseline beta-END levels were higher than in healthy age-matched controls. In seven patients treatment reduced beta-END, whose levels rose in four children. Autistic symptoms were considerably attenuated in all cases, with functional improvements involving several areas. There was a close correlation between the reduction in beta-END levels and the decrease of social withdrawal, and an evident--though weak--correlation between increases in beta-END and decreases in stereotypy and abnormal speech. Both effects persisted after treatment stopped.
1999
Cazzullo AG; Musetti MC; Musetti L; Bajo S; Sacerdote P; Panerai A
European Neuropsychopharmacology
1999
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Journal Article
<a href="http://doi.org/10.1016/s0924-977x(99)00010-3" target="_blank" rel="noreferrer">10.1016/s0924-977x(99)00010-3</a>
Beta-endorphin concentrations in the peripheral blood mononuclear cells of migraine and tension-type headache patients
Female; Humans; Male; Adult; Middle Aged; beta-Endorphin/blood; Biomarkers of Pain; Radioimmunoassay; Leukocytes; Headache/blood; Migraine Disorders/blood; Mononuclear/chemistry
Levels of beta-endorphin in peripheral blood mononuclear cells have been studied as a new approach to investigating opioid tone in migraine and tension-type headache. Sixty-one patients with migraine without aura, 39 with migraine with aura and 23 with episodic tension-type headache were compared with 37 healthy controls. Peripheral blood samples were taken from patients not enduring headache attacks and not undergoing prophylactic treatment. A significant reduction in peripheral blood mononuclear cell beta-endorphin concentrations was observed in migraine patients with and without aura, but not in tension-type headache patients. Altered transmitter modulation to peripheral blood mononuclear cells may be the cause of this alteration, which could be part of a more diffuse opioid system derangement in migraine subjects.
1992
Leone M; Sacerdote P; D'Amico D; Panerai AE; Bussone G
Cephalalgia
1992
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Journal Article
<a href="http://doi.org/10.1046/j.1468-2982.1992.1203155.x" target="_blank" rel="noreferrer">10.1046/j.1468-2982.1992.1203155.x</a>
Beta-endorphin levels are reduced in peripheral blood mononuclear cells of cluster headache patients
Female; Humans; Male; Adult; Reference Values; beta-Endorphin/blood; Cluster Headache/blood; Monocytes/metabolism
Opioid system hypofunction has been postulated in cluster headache (CH) on the basis of reduced opioid levels found in the cerebrospinal fluid (CSF). In this study beta-endorphin levels were monitored in the peripheral blood mononuclear cells of 65 episodic CH patients (32 in remission and 33 in cluster period) and 50 healthy controls. Beta-endorphin levels were significantly lower than controls in CH patients experiencing both phases of the illness (ANOVA, p < 0.0001). The persistence of this abnormality during pain-free remission suggests a primary alteration in the regulation of beta-endorphin in peripheral blood mononuclear cells. We speculate that these findings reflect reduced CNS levels of beta-endorphin in CH.
1993
Leone M; Sacerdote P; D'Amico D; Panerai AE; Bussone G
Cephalalgia
1993
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Journal Article
<a href="http://doi.org/10.1046/j.1468-2982.1993.1306413.x" target="_blank" rel="noreferrer">10.1046/j.1468-2982.1993.1306413.x</a>
Decreased levels of beta-endorphin in circulating mononuclear leukocytes from patients with acute myocardial infarction
Female; Humans; Male; Middle Aged; Biomarkers of Pain; Biomarkers Reference List; Leukocytes; beta-Endorphin/blood/immunology; Myocardial Infarction/blood; C-Reactive Protein/analysis; Mononuclear/metabolism
Lymphocytes can be activated to produce and release opioid peptides. We investigated the levels of immunoreactive beta-endorphin in peripheral blood mononuclear cells from 11 patients with acute myocardial infarction. The concentrations of beta-endorphin in mononuclear leukocytes of 30.2 +/- 6.9 pg/10(6) cells on admission were in the normal range of 20-40 pg/10(6) cells and decreased significantly to 6.9 +/- 1.9 pg/10(6) cells after 48 h (p < 0.05). Decreased levels of mononuclear leukocyte-associated beta-endorphin in acute myocardial infarction may be due to the release of endogenous opioid after stimulation by stress and acute-phase reactants and play a role in inflammation and pain.
1998
Buratti T; Schratzberger P; Dunzendorfer S; Manfreda SE; Pechlaner C; Joannidis M; Sacerdote P; Panerai AE; Wiedermann CJ
Cardiology
1998
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Journal Article
<a href="http://doi.org/10.1159/000006815" target="_blank" rel="noreferrer">10.1159/000006815</a>
Beta-endorphin and cholecystokinin 8 concentrations in peripheral blood mononuclear cells of autistic children
Child; Female; Humans; Male; Reference Values; adolescent; Preschool; infant; beta-Endorphin/blood; Biomarkers of Pain; Child Development Disorders; Sincalide/blood; Monocytes/metabolism; Autistic Disorder/blood/diagnosis/psychology; Pervasive/blood/diagnosis/psychology
beta-Endorphin (beta-EP) and cholecystokinin 8 (CCK-8) concentrations in peripheral blood mononuclear cells were measured in 12 drug-free autistic (AU) children, in 10 drug-free children with pervasive developmental disorders (PDD) and in 11 healthy controls. The aim of the study was to see whether or not there was an alteration of beta-EP and CCK-8 concentrations in this peripheral compartment, in which it has been suggested that secretion and regulation of the two peptides mimic those of neurons in the central nervous system. Mean beta-EP values were significantly higher in AU than in PDD and control children, while there were no differences in CCK-8 values of the three groups.
1997
Brambilla F; Guareschi-Cazzullo A; Tacchini C; Musetti C; Panerai AE; Sacerdote P
Neuropsychobiology
1997
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Journal Article
<a href="http://doi.org/10.1159/000119322" target="_blank" rel="noreferrer">10.1159/000119322</a>