beta-endorphin and Dermatitis--Atopic

Alterations in the hypothalamic-pituitary-adrenal (HPA) system are well documented in affective disorders. In depression these include increased secretion of cortisol, an insufficient suppressibility of cortisol by dexamethasone, a blunted corticotropin (ACTH) response to corticotropin-releasing hormone (CRH) and a dysfunction of the glucocorticoid receptor. Patients with atopic eczema, a common chronic skin disease, show seasonal variations in disease activity, symptoms of minor depression and immunological disturbances similar to those seen in patients with depression. To explore the integrity of the HPA system integrity in individuals with atopic eczema we studied the 24-h cortisol secretion and the cortisol, ACTH and beta-endorphin responses to CRH in such individuals and in healthy controls matched for sex and age. The 24-h secretion of cortisol did not differ between the patients with atopic eczema and the controls. The net response to CRH administered as a 100 micrograms i.v. bolus was significantly attenuated for both cortisol (24,235 +/- 12,443 vs. 47,019 +/- 34,515 nmol.min/dl; p < .03) and for ACTH (546 +/- 205 vs. 727 +/- 310 pmol.min/l; p < .05) in the patient group, whereas the beta-endorphin response did not differ between the groups (1072 +/- 448 vs. 1603 +/- 421 nmol.min/l). The blunted response of cortisol and ACTH cannot be explained by hypercortisolism as it is the case in major depression. Rather, it may be related to a prolonged underexposure to hypothalamic CRH or to an increased sensitivity of glucocorticoid feedback inhibition.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Circadian Rhythm; Corticotropin-Releasing Hormone; Dermatitis, Atopic; Female; Humans; Hydrocortisone; Male

Itch is the cardinal symptom of atopic dermatitis (AD). β-Endorphin, a neuropeptide, is increased in both AD skin and sera. Interleukin (IL)-31, an itch-relevant cytokine, activates IL-31 receptors in keratinocytes. However, how IL-31 and β-endorphin interact in AD skin remains elusive.. To investigate the mechanistic interaction of IL-31 and β-endorphin in AD.. This was a prospective cross-sectional study. We recruited adult patients with AD and controls according to Hanifin's AD criteria. Serum levels of IL-31 and β-endorphin were measured by enzyme-linked immunosorbent assay. Expressions of IL-31 receptor A (IL-31RA) and β-endorphin in the skin were assessed by immunohistochemistry. Their expression in the skin and blood was compared and correlated in patients with AD and in controls. We also treated primary keratinocytes with IL-31 and measured calcium influx, β-endorphin production and signalling pathways to define their mechanistic interactions.. β-Endorphin was increased in the supernatant from IL-31-treated keratinocytes. IL-31 receptor activation resulted in calcium influx and STAT3 activation; pretreatment with STAT3 inhibitor stopped the increase of β-endorphin. Notably, either replacement of extracellular calcium or treatment with 2-aminoethoxydiphenyl borate, an inhibitor for the store-operated channel, blocked STAT3 activation. We found higher levels of blood β-endorphin and IL-31, which were significantly correlated, in patients with AD. Moreover, IL-31RA and β-endorphin were increased and colocalized both in AD human skin and TPA-painted mouse skin.. IL-31 receptor activation in keratinocytes induces calcium influx and STAT3-dependent production of β-endorphin. These results might contribute to an understanding of the regulatory mechanisms underlying peripheral itch.

Topics: Adult; Animals; beta-Endorphin; Biomarkers; Blotting, Western; Calcium; Case-Control Studies; Cross-Sectional Studies; Dermatitis, Atopic; Enzyme-Linked Immunosorbent Assay; Epidermis; Humans; Interleukins; Keratinocytes; Mice; Prospective Studies; Real-Time Polymerase Chain Reaction; STAT3 Transcription Factor

Atopic dermatitis is well known to exacerbate by stress. How the influence of exercise stress on the skin symptoms in patients with atopic dermatitis has not been clarified. The purpose of our research is to investigate how different strength of exercise stress acts on atopic dermatitis. Specific pathogen-free (SPF) and conventional NC/Nga male mice were used for the experiments. Conventional mice but not SPF group spontaneously develop dermal symptom similar to that of patients with atopic dermatitis at their age of 7 weeks. They were given two types of stress, mild (20 m/min for 60 min) or strong exercise (25 m/min for 90 min), using a treadmill four times per day. The dermal symptom of the conventional group was strongly exacerbated by strong exercise but ameliorated by mild exercise. Under the standard experimental conditions, plasma concentrations of α-melanocyte-stimulating hormone (α-MSH), transforming growth factor-β (TGF-β) and substance P in conventional mice increased markedly with concomitant exacerbation of the symptom. The plasma concentrations of these proteins elevated after strong exercise but decreased after mild exercise. Under the conventional conditions, plasma levels of β-endorphin increased with time by some mechanisms enhanced by the mild exercise. These observations suggested that exercise-induced stress significantly affect the symptom of atopic dermatitis in a pivotal manner depending on the plasma levels of TGF-β, α-MSH, substance P and β-endorphin.

Topics: Adrenocorticotropic Hormone; alpha-MSH; Animals; beta-Endorphin; Dermatitis, Atopic; Exercise Test; Immunoglobulin E; Male; Mice; Mice, Inbred Strains; Physical Conditioning, Animal; Skin; Specific Pathogen-Free Organisms; Stress, Physiological; Substance P; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Atopic dermatitis (AD) is a disease of increasing incidence among paediatric patients. Among the factors involved in its pathogenesis is the alteration of the immune response, and so the objective of this study was to evaluate the involvement of certain neuroendocrine factors with immune properties in the development of the disease. Fifty-five subjects were selected and divided into the following three groups: healthy subjects, those diagnosed with symptomatic AD and those with asymptomatic AD. Plasma levels of melatonin and beta-endorphins were measured by radioimmunoassay, in serum samples obtained at 9 am and 9 pm, with two samples being obtained from each of the patients and controls. In the phases of AD outbreaks, there is a reduction in the serum levels of both melatonin and beta-endorphin. In the case of melatonin, the difference is statistically significant only during the day, although nocturnal levels are greater for both hormones. In AD, a central neuroendocrine dysfunction may be a primary pathogenic event. Our hypothesis is that the physiological nocturnal peak of melatonin due to pineal gland production may mask the decline of melatonin of possibly extrapineal (immunological) origin during episodes of dermatitis outbreaks. Further studies are required, particularly of neurovegetative and hormonal aspects, to better define this process. Such a definition would also be of therapeutic interest.

Topics: Adolescent; Adult; Aged; beta-Endorphin; Child; Child, Preschool; Circadian Rhythm; Dermatitis, Atopic; Female; Humans; Male; Melatonin; Middle Aged; Neurosecretory Systems; Pineal Gland

Although itch is the predominant symptom of atopic dermatitis (AD), it is poorly characterized and subjective. The objective assessment of itch intensity is important for treatment and follow-up in patients with AD.. To determine what objective clinical parameter(s) could be used as biomarker(s) for itch intensity in patients with AD.. This is a retrospective and cross-sectional study. Seventy-five patients, aged 7 months-49 years with equal sex ratio, were enrolled in 2000 according to criteria proposed by Hanifin and Rajka. Thirty-five age- and sex-matched subjects who visited the dermatological clinic but were otherwise healthy served as controls. Subjective itch intensity was divided into four grades of severity. Disease severity was measured by SCORAD index, which also includes itch intensity as part of the measurement. Transepidermal water loss (TEWL) and skin surface pH were measured by noninvasive methods in clinically normal skin on the forearm. Serum beta-endorphin and vasoactive intestinal peptide (VIP) were determined by radioimmunoassay. Ordinal logistic regression was used to assess the trend of the subjective itch intensity and SCORAD index by serum IgE, beta-endorphin, VIP, TEWL and skin pH.. There were significant trends for itch intensity with IgE, beta-endorphin and TEWL. After adjustment for sex, age and other variables, the odds ratio (OR) for itch intensity by log IgE, beta-endorphin and TEWL was 2.103 [95% confidence interval (CI) 1.222-3.618], 1.100 (95% CI 1.005-1.203) and 1.081 (95% CI 1.009-1.158), respectively. The OR for disease severity by log IgE, beta-endorphin and TEWL was 2.250 (95% CI 1.149-4.407), 1.156 (95% CI 1.086-1.231) and 1.071 (95% CI 0.971-1.182), respectively. In contrast, there was no association between serum VIP concentration and itch intensity.. Beta-endorphin and IgE are both useful biomarkers for itch and disease severity in patients with AD, while TEWL is a good biomarker for itch intensity. These biomarkers provide a way to assess the itch intensity in patients with AD.

Topics: Adolescent; Adult; beta-Endorphin; Biomarkers; Child; Child, Preschool; Dermatitis, Atopic; Epidemiologic Methods; Female; Humans; Hydrogen-Ion Concentration; Immunoglobulin E; Infant; Male; Middle Aged; Pruritus; Severity of Illness Index; Vasoactive Intestinal Peptide; Water Loss, Insensible

Atopic eczema is a chronic inflammatory skin disease which shares some psychological and neuroendocrine disturbances with patients suffering from depression. In view of recent findings of an attenuated response of the hypothalamic-pituitary-adrenal (HPA) system in patients with atopic eczema during a human corticotropin-releasing hormone (hCRH) challenge paradigm fourteen consecutive non-specifically trained in-patients with atopic eczema (8 men, 6 women) and an age-matched control group (8 men, 6 women) performed exhausting incremental graded bicycle exercise to evaluate cortisol, adrenocorticotropin (ACTH), beta-endorphin, epinephrine and norepinephrine releases induced by physical stress. The exercise yielded significant increases in cortisol, ACTH, beta-endorphin, epinephrine and norepinephrine concentrations in both groups. Patients with severe eczema displayed a significantly lower increase in norepinephrine levels when compared with the less affected patient group. In contrast to the challenge with exogenous hCRH no substantial difference in the net responses of ACTH and cortisol could be detected between patients with atopic eczema and controls using the physical stress paradigm. These substantial differences in the net outcome between both challenges may be related to the potential synergizing effects of various neuropeptides, e.g. CRH and vasopressin, when activating the HPA system by challenges at a suprapituitary site which may override subtle disturbances in the responsivity of the HPA system as revealed by CRH challenge alone in patients with atopic eczema.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Corticotropin-Releasing Hormone; Dermatitis, Atopic; Epinephrine; Exercise Test; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Kinetics; Male; Norepinephrine; Physical Exertion; Pituitary-Adrenal System; Reference Values; Stress, Physiological

Serum beta-endorphin was measured by radioimmunoassay in 25 patients with atopic dermatitis and 100 healthy subjects. The neuropeptide was found to be markedly (p < 0.001) increased in patients with atopic dermatitis (9.2 +/- 3.4 pg/ml) as compared to normal controls (6.1 +/- 1.5 pg/ml). A correlation between increased serum beta-endorphin concentration and some clinical parameters of the disease has been found. The statistically significant elevation of beta-endorphin was found in patients with widespread atopic dermatitis lesions involving more than 20% of the skin surface (11.1 +/- 3.6 pg/ml), a high disease severity score (10.7 +/- 3.7 pg/ml), and previous bronchial asthma symptoms (11.6 +/- 3.1 pg/ml). A possible explanation of increased beta-endorphin is either its generation in atopic dermatitis lesions by inflammatory cells or activation of pituitary-adrenal axis by psychoneural factors in the mechanism of chronic stress.

Topics: Adolescent; Adult; Aged; Asthma; beta-Endorphin; Body Surface Area; Case-Control Studies; Dermatitis, Atopic; Female; Humans; Male; Middle Aged; Pituitary-Adrenal System; Stress, Physiological

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

A 21-year-old female with atopic dermatitis showed "dependence" on very hot hot-spring bathing. Her skin disease had been refractory to various treatments including steroid therapy for a long time. Without medical supervision she took four 3-minute 47 degrees C hot-spring baths daily for a month for the purpose of improving her skin symptom. Subsequently, she could not stop bathing in very hot hot-spring water of her own will. However, a month's isolation in a hospital relieved her of the situation. The mechanism of the dependence on very hot hot-spring bathing may be explained by a transient rise in the plasma beta-endorphin level due to hyperthermal stress.

Topics: Adult; Balneology; beta-Endorphin; Dermatitis, Atopic; Female; Humans; Length of Stay; Time Factors

Atopic dermatitis (AD) is a pruritic cutaneous inflammatory condition. As pruritus and pain are very close symptoms, we determined the beta-endorphin serum concentrations in 21 atopic children with pruritus (group A) and 20 children with healed AD without pruritus (group B). Twenty-five healthy school children were the control group. The beta-endorphin serum concentrations (14.95 +/- 2.75 pmol/l) in group A were statistically (P < 0.001) elevated in our patients compared to controls (8.85 +/- 2.39 pmol/l) whereas these in group B were not elevated (9.4 +/- 2.46 pmol/l). We suggest that the elevated beta-endorphin concentrations in atopic patients with pruritus confirm the hypothesis that there is an increased activity of their opioid system and that an opioid antagonist might block itching which is their major clinical symptom.

Topics: beta-Endorphin; Child; Child, Preschool; Dermatitis, Atopic; Female; Humans; Male; Pruritus

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

Topics: Acupuncture Therapy; Adolescent; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Chronic Disease; Cyclic AMP; Dermatitis, Atopic; Female; Humans; Male; Middle Aged