beta-endorphin and Psoriasis

Psoriasis is a complex, multifactorial inflammatory skin disease with genetic and environmental interactions. Patients with psoriasis exhibit erythematous plaques with itch, but the mechanisms of psoriatic itch are poorly understood.. This study was performed to investigate epidermal nerve density and opioid receptor levels in psoriatic skin with or without itch.. Twenty-four patients with psoriasis aged between 39 and 82 years were included in this study. The number of epidermal nerve fibres, the levels of semaphorin 3A (Sema3A) and the expression patterns of μ- and κ-opioid systems were examined immunohistologically in skin biopsies from psoriatic patients with or without itch and healthy volunteers as controls.. The number of epidermal nerve fibres tended to increase in approximately 40% of psoriatic patients with itch compared with healthy controls, while such intraepidermal nerves were not observed in other itchy patients. In comparison with healthy controls, Sema3A levels also tended to decrease in the epidermis of psoriatic patients with itch. However, no relationship was found between nerve density and Sema3A levels in the epidermis of psoriatic patients with itch. The levels of μ-opioid receptor and β-endorphin in the epidermis were the same in healthy controls and psoriatic patients with or without itch. The levels of κ-opioid receptor and dynorphin A were significantly decreased in the epidermis of psoriatic patients with itch compared with healthy controls.. Based on Sema3A levels in the epidermis, epidermal opioid systems, rather than hyperinnervation, may be involved in the pathogenesis of psoriatic itch.

Topics: Adult; Aged; beta-Endorphin; Biopsy, Needle; Case-Control Studies; Dynorphins; Epidermis; Female; Humans; Immunohistochemistry; Male; Middle Aged; Nerve Fibers; Pruritus; Psoriasis; Receptors, Opioid; Semaphorin-3A

Previous studies suggested that beta-endorphin has a pathogenic role in psoriasis: its increased plasma concentration may play a role in the neuroimmunological processes in the pathomechanism of the disease, and plasma beta-endorphin levels should reflect the changes in the patients' skin status. The purpose of this study was to investigate the changes of peripheral blood beta-endorphin levels in psoriatic patients in conjunction with changes in their skin symptoms after synchronous balneophototherapy.. With synchronous balneophototherapy, 12 patients with extended skin symptoms of psoriasis were treated. The therapy followed the Regensburg protocol, consisting of a basic course of 35 sessions. Patients' skin status was characterized by evaluating the Psoriasis Area and Severity Index score before and after the therapy course. Blood samples were taken before treatment, and 1 day after the last session, with symptom-free skin. Plasma beta-endorphin levels were measured by a specific radioimmunoassay developed by the authors.. There was no significant change in plasma levels of beta-endorphin after clinical clearance of psoriatic skin symptoms.. In this non-randomized, uncontrolled study no significant difference could be detected between plasma beta-endorphin levels before and after a basic course of synchronous balneophototherapy in patients with psoriasis. Although beta-endorphin has many neuroimmunological effects, the changes of its plasma level do not consistently reflect the skin status. Inflammation in psoriatic skin lesions is probably not mediated directly by circulating beta-endorphin.

Topics: Adult; Balneology; beta-Endorphin; Combined Modality Therapy; Female; Humans; Male; Middle Aged; Phototherapy; Psoriasis; Radioimmunoassay

It has been reported that opioid peptides modulate the differentiation of normal human keratinocytes and that mu-opiate receptors are expressed in human epidermis. The regulation of keratinocyte differentiation is particularly important in psoriasis, and one of the markers for hyperproliferative and differentiating skin diseases is cytokeratin 16. The finding that the endogenous mu-opiate receptor ligand beta-endorphin is increased in serum of patients with psoriasis indicates that the mu-opiate system may play an important role in the pathophysiology of the skin. In this study, we addressed the question whether there is a link between mu-opiate receptor regulation and cytokeratin 16 expression in normal and psoriatic skin. Firstly, we demonstrate that beta-endorphin concentrations between 16 and 1000 nM significantly downregulate mu-opiate receptor expression in epidermis of cultured human skin after 48 h. Secondly, we show that beta-endorphin regulates cytokeratin 16 expression in the epidermis of skin organ cultures exposed to 41-125 nM beta-endorphin for 48 h, leading to elevated cytokeratin 16 production. As expected, the expression of cytokeratin 16 was detected primarily in the suprabasal layer. The same pattern was observed in psoriatic lesional skin, i.e., mu-opiate receptor expression was significantly downregulated and cytokeratin 16 expression upregulated. These results suggest that the mu-opiate receptor system and its ligand beta-endorphin are involved in the pathogenesis of psoriasis, especially in terms of differentiation.

Topics: beta-Endorphin; Down-Regulation; Humans; Immunohistochemistry; Keratins; Organ Culture Techniques; Psoriasis; Receptors, Opioid; Skin; Up-Regulation

An increased concentration of neuropeptides in psoriatic lesional skin may be responsible for alterations in the neurogenic erythematous response and transmission of stimuli through sensory nerve fibers (sensation of pruritus).. Increasing doses of capsaicin from 0.125 to 4 micrograms/cm2 were applied to nonlesional psoriatic skin to establish the minimal dose that induced the substance P-mediated neurogenic response in 30 patients with psoriasis. Plasma beta-endorphin was quantitated in 71 psoriatics by radioimmunoassay using NEN 1251-RIA kit.. The mean beta-endorphin concentration was increased about 2-fold compared to normals, whereas doses of capsaicin needed to induce erythema were higher (1-4 micrograms/cm2) in psoriatics (mainly in patients with type II psoriasis) than in healthy subjects (0.125-0.25 microgram/cm2).. The data indicate that increased beta-endorphin in psoriatic skin might affect both substance P-mediated neurogenic inflammation and transmission of sensory stimuli due to local antinociceptive effects of this opioid. The differences in the neurogenic response in type I and II psoriasis may be related to the degradation of substance P and beta-endorphin by neutral proteinases in the lesional skin.

Topics: beta-Endorphin; Capsaicin; Dermatitis, Atopic; Humans; Neuropeptides; Psoriasis; Scleroderma, Systemic; Skin; Substance P

The immune system is important in the pathogenesis of psoriasis and emotional stress has precipitated psoriasis in many patients. Neuropeptides, alpha-Melanocyte stimulating hormone (alpha-MSH), beta-endorphin, met-enkephalin and substance P (SP) act as immunomodulators, and their secretion increases during periods of stress. To see whether these neuropeptides themselves might be related to psoriasis and/or to the aggressiveness of the disease, we evaluated the plasma neuropeptide levels in 13 patients with active psoriasis (patients with new lesions and/or pre-existing lesions that had become larger during the month before the study), in 11 patients with stable psoriasis and in 10 healthy controls. Plasma concentrations of neuropeptides were evaluated by RIA (immunoradiometric assay for beta-endorphin). Data were compared by the Student t-test for unpaired data. There were no significant differences between the plasma levels of any of the neuropeptides between active psoriatic patients and stable psoriatic patients, nor between the plasma levels of neuropeptides of psoriatic patients and those of control subjects. It seems unlikely that circulating neuropeptide levels are of primary importance in the manifestation of the psoriatic skin lesions.

Topics: Adult; alpha-MSH; beta-Endorphin; Enkephalin, Methionine; Humans; Male; Middle Aged; Neuropeptides; Psoriasis; Substance P

Serum beta-endorphin was quantified by radioimmunoassay in 71 patients with psoriasis vulgaris, other chronic inflammatory skin diseases with T-cell infiltrates [atopic dermatitis (n = 25), and systemic sclerosis (n = 34)], and 100 healthy subjects. The neuropeptide was found to be markedly (P < 0.001) increased in patients with psoriasis (14.4 pg/ml), atopic dermatitis (9.2 pg/ml) and systemic sclerosis (9.8 pg/ml) compared with normal controls (6.1 pg/ml). The highest values of beta-endorphin were found in patients with actively spreading plaque psoriasis (17.3 pg/ml), whereas lesion-free patients showed a reduction in neuropeptide concentration (10.2 pg/ml). The levels were much higher in patients with widespread psoriatic lesions (> 60% body surface; 16.2 pg/ml), which lasted longer than 3 months (15.8 pg/ml), whereas neither the presence of stress nor itching correlated with the serum peptide concentration. Our data suggest that beta-endorphin is produced in psoriatic lesions by inflammatory cells, rather than the increased levels being the result of activation of the pituitary-adrenal axis by chronic stress. The generation of neuropeptide in psoriatic lesions and its antinociceptive effect on the peripheral sensory nerves might explain why pruritus is a relatively rare phenomenon in psoriasis.

Topics: Acute Disease; Adolescent; Adult; Aged; beta-Endorphin; Dermatitis, Atopic; Female; Humans; Male; Middle Aged; Psoriasis; Radioimmunoassay; Scleroderma, Systemic

We investigated the presence of proopiomelanocortin (POMC) products in sections of skin from normal subjects and patients with neoplastic and non-neoplastic cutaneous disorders. Antibodies specific against adrenocorticotropin, beta-melanotropin, and beta-endorphin were used for detection and characterization of cell types bearing POMC peptides. POMC products were not observed in sections of normal skin from the corporal (non-scalp) areas (six cases), whereas the hair follicles of scalp skin exhibited positive immunostains that were readily apparent (four cases). POMC products were frequently detected in corporal skin affected by diseases (13 of 26 cases), for example, psoriatic keratinocytes, the inflammatory infiltrate in scarring alopecia, nevocytes, the epithelial cell nests of basal cell carcinoma, and melanoma cells. Further tests were performed in keloids, a primary reactive skin disorder, to evaluate whether POMC accumulation represented a disease-related phenomenon or an expression of normal cutaneous reactivity. POMC products were consistently detected (10 of 11 cases) in the keratinocytes and mononuclear cells at keloid lesions. Thus these observations indicate that POMC products may accumulate locally in lesional skin representing, presumably, a novel cutaneous response to injury. The broad spectrum of POMC products detected suggests that these arise from production in situ (expression of the POMC gene itself) by human skin.

Topics: Adrenocorticotropic Hormone; beta-Endorphin; Carcinoma, Basal Cell; Cytoplasm; Humans; Immunohistochemistry; Keratinocytes; Melanocyte-Stimulating Hormones; Melanoma; Nevus; Pro-Opiomelanocortin; Psoriasis; Scalp; Skin; Skin Diseases; Skin Neoplasms