beta-endorphin and Multiple-Sclerosis

Since the earliest descriptions psychological and physical stress has been considered a controversial but potentially important factor in the onset and course of multiple sclerosis (MS). During recent years it has become clear that MS patients benefit from physical exercise as performed in aerobic training. As acute exercise has profound effects on immune and endocrine parameters we studied endocrine and immune response to standardized physical stress in MS within a study of aerobic training. Fifteen MS patients completed an eight-week aerobic training program, 13 patients were part of a wait-control group. Twenty healthy controls were recruited as well. A step-by-step bicycle ergometry was performed to determine individual exertion levels. For the endurance test patients exercised at 60% VO2 max for 30 min. Blood samples were drawn before, directly after and 30 min after completion of the exercise. Heart rate and lactate increased in all groups (p<.0001). We furthermore saw significant increases in endocrine parameters (epinephrine, norepinephrine, ACTH, and beta-endorphin; all p<.0001) in healthy individuals and in MS patients but without a differential effect. Whole-blood stimulated production of IFN-gamma (IFNgamma) was induced similarly in all groups (p<.01). TNF-alpha (TNFalpha) and IL-10 were less inducible in MS patients (trend). From these data we could not demonstrate a proinflammatory immune deviation in response to physical stress in MS. The observed trend of hyporesponsive TNFalpha and IL-10 responses in MS warrants further investigation.

Topics: Adrenocorticotropic Hormone; Adult; Analysis of Variance; beta-Endorphin; Cytokines; Epinephrine; Exercise; Exercise Test; Female; Heart Rate; Humans; Hydrocortisone; Interferon-gamma; Interleukin-10; Lactic Acid; Male; Multiple Sclerosis; Norepinephrine; Physical Fitness; Reference Values; Stress, Physiological; Tumor Necrosis Factor-alpha

In a double-blind placebo-controlled crossover study of ten patients with multiple sclerosis, we found amantadine hydrochloride therapy to be effective in improving fatigability in six. Administration of the drug was associated with significantly higher levels of beta-endorphin-beta-lipotropin and responders had significantly higher levels than nonresponders. Lactate levels were significantly higher and pyruvate levels lower in nonresponders. Amantadine given for fatigue to patients with multiple sclerosis is associated with measurable changes in levels of metabolites and peptides in the circulation.

Topics: Amantadine; beta-Endorphin; beta-Lipotropin; Disability Evaluation; Fatigue; Humans; Lactates; Lactic Acid; Multiple Sclerosis; Pyruvates; Pyruvic Acid

Multiple sclerosis (MS) is an autoimmune-mediated degenerative disorder with increased peripheral inflammation disrupting the blood brain barrier. With increasing MS-related healthcare costs, the requirement to validate minimally invasive biomarkers has become imperative.. Relapsing-remitting MS patients on disease modifying therapies were consented at the Penn State Health MS Clinic to provide blood samples for analyses of serum cytokines and endogenous opioid peptides, as well as to complete the MSQOL-54 survey.. Serum OGF levels in MS patients on glatiramer acetate (mean = 326 pg/ml), dimethyl fumarate (mean = 193.3 pg/ml) and natalizumab (mean = 393.4 pg/ml) were significantly elevated (p < 0.01) compared to healthy controls (mean = 98.46 pg/ml). Individuals with elevated OGF levels also had increased levels of TNFα (r = 0.78) and IL-17A (r = 0.81). Only patients treated with glatiramer acetate had significant (p < 0.01) elevations in serum β-endorphin levels. Analyses of MS-QoL 54 data showed no significant differences in physical or mental composite scores between treatment groups. However, serum levels of β-endorphin had a direct correlation with physical health composite score (r = 0.70) in all treatments. Serum vitamin D levels had an indirect relationship with 25-foot walk test times (r = 0.47).. Both regression and cohort data suggest that serum levels of OGF, β-endorphin, and vitamin D are potential biomarkers for physical disease status in MS.

Topics: beta-Endorphin; Biomarkers; Glatiramer Acetate; Humans; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physical Functional Performance; Quality of Life; Receptors, Opioid

Previously, we demonstrated that electroacupuncture (EA) decreased lymphocyte infiltration into the spinal cords of rats presenting with experimental autoimmune encephalomyelitis (EAE), a disease model used in the study of multiple sclerosis (MS). The aim of this study was to characterize the effects of EA on the EAE. Female Lewis rats were divided into either CFA, EAE, EA, or injection with naloxone after electroacupuncture (NAL) groups. Electroacupuncture was administered every day for 21 days. To evaluate proliferation and apoptosis, lymphocytes from rats presenting with EAE were collected and cultured with β-endorphin. Immunohistochemisty, flow cytometry and radio-immunity methods were applied to detect the expression of β-endorphin. Results presented in this report demonstrate that the beneficial anti-inflammatory effects of EA on EAE were related to β-endorphin production that balances the Thl/Th2 and Th17/Treg responses. These results suggest that β-endorphin could be an important component in the development of EA-based therapies used for the treatment of EAE.

Topics: Animals; Apoptosis; beta-Endorphin; Cell Proliferation; Electroacupuncture; Encephalomyelitis, Autoimmune, Experimental; Female; Humans; Multiple Sclerosis; Naloxone; Rats; Rats, Inbred Lew; T-Lymphocytes, Regulatory; Th1-Th2 Balance; Th17 Cells

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.

Topics: Adult; beta-Endorphin; Brain; Female; Humans; Leukocytes, Mononuclear; Magnetic Resonance Imaging; Male; Middle Aged; Multiple Sclerosis; Phenotype

Prolonged clinico-immunological observation of 85 patients with definite multiple sclerosis (MS) was performed in order to elucidate the connections between the clinical and immune state. A battery of immunological investigations was performed, including estimation of T-cell subpopulations in blood and cerebrospinal fluid (CSF); proliferative responses of circulating lymphocytes to mitogens, recombinant interleukin-2 (rIL2) and myelin basic protein levels in different culture conditions; levels of immunoglobulin (Ig) in sera and CSF, and of Ig production in vitro; indices of IL2 synthesis and IL2 sensitivity; production of prostaglandin E2 and tumour necrosis factor (TNF) alpha by monocytes and levels of beta-endorphin in sera and supernatants phytohaemagglutinin of (PHA)-activated cells. Clinical observation was performed periodically using Kurtzke scales and was supplemented by repeated recording of evoked potentials and magnetic resonance imaging. Initial investigations showed specific differences between patients with MS and the control groups (donors and patients with other neurological disorders of the same age). Correlative and regressive analyses showed no association between immunological and clinical parameters at the initial investigation, although immunological indexes were inter-related, and indicated specific alterations in immunoregulation in MS. Retrospective analysis revealed associations between the clinical status of patients with MS and their previous immune status. Evidence of cell activation--including a decreased percentage of circulating cells with differential antigens, lower cell mitogen-induced proliferative responses in vitro, with restoration following the addition of autoserum, greater IL2 sensitivity, and increased TNF-alpha production by macrophages--often predicted the clinical manifestation of deterioration. It is proposed that the immunopathological process in MS has a number of stages with characteristic features, and that progression from one stage to another can be subclinical. No single immunological index can be used to determine stage. Only systemic alterations reflect the real situation, whilst every patient has some abnormalities. A system of clinico-immunological monitoring could severe as the basis for a new approach to the dynamic treatment of MS.

Topics: Adolescent; Adult; beta-Endorphin; Female; Humans; Immunoglobulin G; Interleukin-2; Lymphocyte Activation; Male; Middle Aged; Multiple Sclerosis; T-Lymphocyte Subsets; Tumor Necrosis Factor-alpha

Topics: Adult; alpha-MSH; beta-Endorphin; Female; Humans; Immunoassay; Male; Multiple Sclerosis; Pro-Opiomelanocortin

Twenty-five patients with chronic progressing multiple sclerosis were examined for the content of beta-endorphin in blood serum, supernatants of activated lymphocytes and CSF by RIA. At the same time the parameters of cellular immunity were appraised. Different relations were discovered between cellular immunity and the content of beta-endorphin in biological fluids which may play a material part in the pathogenesis of multiple sclerosis.

Topics: Adult; beta-Endorphin; Chronic Disease; Culture Media; Female; Humans; In Vitro Techniques; Interleukin-2; Leukocyte Count; Lymphocyte Activation; Male; Middle Aged; Multiple Sclerosis; Phytohemagglutinins; T-Lymphocytes

Using radioimmunoassay the authors studied concentrations of beta-endorphine and metenkephalin in the cerebrospinal fluid (CSF) of 65 patients with various diseases of the central nervous system (CNS)--hereditary extrapyramidal disorders, disseminated sclerosis (DS), lateral amyotrophic sclerosis (LAS), spinal tumours, senile dementia, some CNS impairments of inflammatory nature. Patients with spinal tumours showed a 4-14-fold elevation in metenkephalin levels along with a comparatively high content of beta-endorphine. In senile dementia, the concentration of both peptides was lowered. In hereditary extrapyramidal diseases, the levels of beta-endorphine were also low, while there was no concomitant decrease in the metenkephalin concentration.

Topics: Amyotrophic Lateral Sclerosis; beta-Endorphin; Central Nervous System Diseases; Chronic Disease; Dementia; Endorphins; Enkephalin, Methionine; Humans; Multiple Sclerosis; Radioimmunoassay; Spinal Cord Neoplasms