Neuropeptides and general neuronal marker in psoriasis an immunohistochemical study

Nerve fibres immunoreactive to antibodies to vasoactive intestinal polypeptide (VIP) and substance P (SP) were increased in lesional psoriatic skin when assessed semi-quantitatively. Biopsies from psoriatic plaques on the arm were studied in 13 patients and compared with biopsies from non-lesional areas (in three of the same psoriatic subjects) and from normal skin in seven non-psomtic controls. Immunohistochemical methods were used on cryocut skin sections to demonstrate the neuropeptides SP, VIP, calcitonin gene-related peptide and neuropeptide Y, and the general neuronal marker protein gene product (PGP) 9.5. The immunofluorescence was examined by semiquantitative and, for PGP 9.5, by quantitative methods. VIP reactive nerve fibres were increased at areas of eccrine sweat glands throughout the dermis, at the dermo-epidermal junction, and in the epidermis, in psoriasis lesional skin. SP reactive nerve fibres were increased at the dermo-epidermal junction, where the nerves ran parallel with and perpendicularly through the junction. PGP 9.5 reactive nerve fibres showed an increase at the dermo-epidermal junction, in the papillary dermis, and at the eccrine sweat glands in lesional psoriatic skin but not in non-lesional, or in control skin. These findings support the hypothesis that neuropeptides may be involved in the pathogenesis of psoriasis.     

白癜风皮损中NPY VIP和SP的研究

目的 探讨NPY（神经肽Y）、VIP（血管活性肠肽）、SP（神经肽P物质）在白癜风发病机制中的作用。方法 采用SABC免疫组化法对20例白癜风患者（活动期10例，稳定期10例）的皮损、非皮损区以及10例正常人皮肤中的NPY、VIP和SP进行研究，并测定各组皮肤标本中NPY、VIP及SP的免疫反应性。结果 活动期白癜风皮损中NPY、VIP及SP的免疫反应性明显增强，与正常对照及未受累皮肤比较差异有差异性，NPY与SP的反应在白癜风活动期皮损与稳定期皮损比较差异也有显著性。VIP的免疫反应性在白癜风活动期皮损与稳定期皮损中相比稍增强，但差异无统计学意义。结论 神经多肽与白癜风的发病有关，尤其与白癜风的活动性有关。NPY和SP可能在白癜风的发病机制中也起一定的作用。     

Tissue estimation of protein gene product 9.5 (PGP 9.5) expression and apoptosis in vitiligo

Background  Vitiligo is probably the end result of different interacting processes.
Objective  To determine the possible roles of neural and apoptotic mechanisms in the pathogenesis of vitiligo.
Methods  Fifty-six biopsies from 28 patients with generalized vitiligo (28 from depigmented lesional areas and 28 from clinically nondepigmented skin at the periphery of the same areas) were examined; the panaxonal marker neuropeptide protein gene product 9.5 (PGP 9.5) and apoptosis were investigated using immunohistochemistry.
Results  Statistically significant differences were detected in the numbers of PGP 9.5-positive nerve fibers/axons in the papillary dermis between the center and periphery of the lesions (i.e. increased at the center in comparison with the periphery). A statistically significant inverse association was found between PGP 9.5 immunostaining in the dermis at the lesion center and the duration of the disease. When apoptosis and PGP 9.5 expression were compared, there was an identical distribution of PGP 9.5-positive nerve fibers/axons and apoptotic cells in the epidermis (i.e. basal in the lesion center; diffuse at the lesion periphery).
Conclusions  There is a possible connection between the neural and apoptotic pathogenetic theories of vitiligo.     

Ontogeny of nerves and neuropeptides in skin of rat: An immunocytochemical study

Abstract The sequence of maturation of nerves and appearance of neuropeptides was investigated in skin from fetal and neonatal rats by immunocytochemistry using antisera to protein gene product 9.5, substance P, calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY). Immunoreactivity for PGP 9.5 appeared on fetal day 16 in face and nose, somewhat later (fetal day 19) in paws and tail. The sensory neuropeptides, CGRP/substance P (fetal day 19 and postnatal day 1, respectively) appeared earlier than the autonomic peptides VIP and NPY (postnatal day 7). Thus, the study shows that neuropeptides do not appear simultaneously with nerves and that the development is rostrocaudal.     

Increased sensory neuropeptides in nodular prurigo: a quantitative immunohistochemical analysis

Seven patients with nodular prurigo, five patients with lichenified eczema and seven control volunteers were studied immunohistochemically using antisera to the pan-neuronal marker protein gene product 9.5 (PGP), and the neuropeptides calcitonin gene-related peptide (CGRP), substance P (SP), tyrosine hydroxylase (TH), vasoactive intestinal polypeptide (VIP) and the C-flanking region of neuropeptide Y (C-PON). PGP-, CGRP- and SP-immunoreactivities were also evaluated using image analysis quantification, and the data compared by statistical analysis. No significant changes were noted in the lichenified skin of patients with chronic eczema, compared with the control groups. In contrast, a significant increase in PGP immunoreactive nerve fibers was seen in lesional skin of all nodular prurigo cases studied, when compared with non-lesional skin from the same patient or from control subjects (P < 0.001). In one case massive neural hyperplasia was also identified. Staining for CGRP and SP showed a large increase of immunoreactive nerves in lesional skin of nodular prurigo patients, which closely paralleled that of PGP. Staining with VIP, C-PON and TH was similar in both lesional and non-lesional skin. These results indicate that neural changes in nodular prurigo are associated with an increase of sensory neuropeptides, which could be related to the intense pruritus which accompanies nodular prurigo. The absence of significant changes in lichenified skin suggests that the increase in CGRP- and SP-immunoreactive nerve fibres is a characteristic feature of nodular prurigo and may be important in its pathogenesis.     

PGP 9.5 distribution patterns in biopsies from early lesions of atopic dermatitis

Peripheral nerve fibres are often increased in lesional skin of atopic dermatitis (AD) patients. We attempted to study nerve fibre profiles, using PGP 9.5 as neuronal marker, in early AD lesions in 10 patients, as compared to non-lesional skin in the same patients and skin from healthy controls. The number of PGP 9.5-positive nerve fibre profiles was not different in the biopsies taken from normal-looking AD skin and healthy controls. The total number of PGP 9.5-positive nerve fibre profiles in the whole skin sections was higher in both the epidermis and the dermis in the group of skin biopsies taken from early lesions of AD patients. Further, the number of epidermal PGP 9.5-positive dendritic cells was increased in AD skin. It seems reasonable that PGP 9.5-positive nerve fibres and PGP 9.5-positive dendritic cells have pathological roles in AD. The findings might serve as a basis for further studies in evaluating novel diagnostic and therapeutic approaches.     

Neuropeptides Profile and Increased Innervation in Becker's Nevus

BackgroundMelanocytes are derived from neural crest, and various pigmentary disorders may accompany abnormalities in nerve system or develop following dermatome, suggesting that melanocyte and pigmentation may be closely related to neural factors. There are reports of Becker''s nevus (BN) showing linear and segmental configuration, suggesting the association of BN with nerve system. However, there are no studies regarding the expression of neuropeptides in BN.ObjectiveWe investigated the expression of neuropeptides and innervation in BN.MethodsPolymerase chain reaction (PCR) array of 84 genes related to neuronal process was done. Among the genes with 10-fold or more increase in lesional, real-time PCR was performed for neuropeptide Y (NPY), galanin, neurotensin (NTS) and their receptors skin compared to normal skin. IHC stain was done to look for the expression of NPY, galanin, NTS and their receptors and the distribution of protein gene products (PGP) 9.5 immunoreactive nerve fibers.ResultsPCR array revealed that 16 out of 84 genes related to neuronal process were increased by 10-fold or more in lesional skin. In real-time PCR of NPY, galanin, NTS and their receptors, statistically significant increase of NPY1R (p<0.05) and marginally significant increase of NPY2R, GAL2R, and NTS2R (p<0.1) was verified in lesional skin. In immunohistochemistry, NPY, NPY1R NPY2R, and NTS2R were highly expressed in lesional skin and increased PGP 9.5 immunoreactive linear nerve fibers were found in the epidermis of BN.ConclusionNPY, galanin, NTS and their receptors and increased innervation may play a role in the pathogenesis of BN.     

白癜风患者血浆三种神经肽测定及其临床意义

目的：β内啡肽（β－EP）、神经肽Y（NPY）及降钙素基因相关肽（CGRP）是重要的神经递质,同时也可作为免疫调节因子发挥作用。本研究旨在观察这些神经肽是否可能与白癜风的发病有关。方法：用放射免疫分析法测定40例白癜风处于进展期或稳定期的不同类型患者血浆3种神经肽浓度,并与23例正常对照作比较。结果：寻常型（局限性与泛发性）、节段型、进展期和稳定期白癜风患者血浆β－EP、NPY水平均较正常对照组显著增高;进展期白癜风NPY比稳定期显著提高;泛发性及进展期白癜风血浆CGRP比正常对照组显著增高。结论：结果表明上述三种神经肽与白癜风的发病可能存在一定关系,开发神经肽拮抗剂对于白癜风的治疗可能成为一种新的途径。     

MORPHOLOGIC OBSERVATIONS ON THE DERMAL NERVES IN VITILIGO: AN ULTRASTRUCTURAL STUDY

Background. Vitiligo is a common idiopathic skin disorder. The etiology is unknown, although various hypotheses have been advanced. These include the neuronal hypothesis, where neuronal factors are thought to play a role in the pathogenesis of this disease. Methods. Skin biopsies were taken from marginal and central parts of four vitiligo patients. Biopsies were also taken from nonvitiliginous skin of each patient and from four normal control subjects. Sections were examined under the electron-microscope. Nerve fibers in the superficial dermis were examined. Results. Subtle ultrastructural changes, including regeneration and degeneration, were consistently found in dermal nerves of vitiligo lesions. The most consistent feature, seen in all four vitiligo patients studied (in both lesional and marginal areas), was an increased thickness of the basement membrane of Schwann cells. This change was found in approximately three-quarters of all dermal nerves in vitiligo biopsies, but in only about one-quarter of dermal nerves in normal control skin. About half the abnormal dermal nerves in vitiligo skin showed minor axonal damage, although indicators of regeneration (increased mitochondria and rough endoplasmic reticulum) predominated. The dermal nerves in vitiligo showed no difference in fiber diameter or fiber density in comparison with controls. Conclusions. In vitiligo both axonal degeneration and nerve regeneration may occur, with the latter possibly being a reactive change to earlier axonal damage. These findings support the hypothesis that there is a neuronal component to this disease.     

Mast cells,nerves and neuropeptides in atopic dermatitis and nummular eczema

The association between mast cells and sensory nerves and the distribution of the neuropeptides substance P (SP), vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP) were studied immunohistochemically in lesional and nonlesional skin of 26 atopic dermatitis (AD) and 23 nonatopic nummular eczema (NE) patients. Mast cell-nerve contacts were counted morphometrically and confirmed by confocal laser scanning microscopy. Neuropeptide positivity was assessed semiquantitatively. Dermal contacts between mast cells and nerves were increased in number in both lesional and nonlesional samples of AD and NE when compared to those in normal controls, although only the values in lesional AD reached statistical significance ( P<0.05). Nerve-mast cell contacts in the basement membrane zone were seen practically only in lesional NE. SP and CGRP fibres were prominently increased in lesional samples when compared to their nonlesional controls both in AD and NE in the epidermis and in the papillary dermis. In both AD and NE, only small differences were found regarding VIP positivity in lesional and nonlesional biopsies. The epidermis was devoid of VIP positivity. In conclusion, SP and CGRP but not VIP fibres were more frequent in lesional than in nonlesional papillary dermis of both AD and NE. Since mast cells are also increased in number in lesions of AD and NE, they are able to maintain neurogenic inflammation through activation by SP and CGRP. The increased SP/CGRP nerves in the epidermis of AD and NE lesions may stimulate keratinocytes to release cytokines which affect various cell types enhancing inflammation.     

Occurrence and distribution of neuropeptides in the human skin. An immunocytochemical and immunochemical study on normal skin and blister fluid from inflamed skin

The content and distribution of substance P (SP), somatostatin, vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) in human skin were investigated. Radioimmunoassay was performed on pooled tissue samples from several regions (fingers, toes, axillas and thighs) and on tissue fluid from spontaneous blisters on inflamed skin. Immunocytochemical localization showed all peptides examined except somatostatin to be present in nerve fibers. Nerve fibers storing SP and CGRP, which were found to coexist, were mostly present as free nerve endings in the superficial part of dermis and in epidermis. SP/CGRP fibers were most abundant in fingers and toes. VIP fibers and NPY fibers were localized in the deeper parts of dermis around blood vessels and acini of sweat glands. Also fibers containing these neuropeptides were most common in fingertips and toes. VIP occurred in relatively high amounts also in skin from axilla whereas NPY in this region was below detection limit. Immunoreactive somatostatin was found in low concentrations in tissue extracts and was not present in amounts sufficient for reliable immunostaining. Fluid from spontaneous blisters on inflamed skin contained detectable amounts of all neuropeptides.     

Cutaneous PGP 9.5 distribution patterns in hidradenitis suppurativa

The aim of this study was to investigate the presence and density of the nerve fibre-marker protein gene product 9.5 (PGP 9.5), with immunohistochemistry, in skin from patients with hidradenitis suppurativa (HS). Punch biopsies were obtained from 16 patients; 10 with involvement of the groin and six with axillary disease. Specimens were taken from HS lesions in the groin or axilla, clinically non-involved skin and from 12 healthy control subjects. Coded slides were observed in the microscope and PGP 9.5 positive nerve fibre profiles (profiles) as well as PGP 9.5 positive cells (cells) were counted. The overall impression was that the median number of profiles was decreased in lesional epidermis, yet statistically significant only in the groin (p = 0.0014). The median number of profiles in dermis was significantly decreased in lesional skin of the axilla, whereas in the groin there were contradictory findings with significantly increased number of profiles in upper dermis and non-significant in mid and lower dermis. The number of cells with strong immunofluorescence was few or absent in epidermis, but increased in dermis in the lesional skin. This difference was statistically significant throughout the dermis in specimens from the groin (p < 0.01) and showed the same trend, although not significant, in the axilla. The PGP 9.5 immunofluorescent cells were not yet further investigated, so it is not exactly known what cell type they represent. In conclusion, despite several study limitations, the findings indicate that PGP 9.5 positive nerve fibres could be involved in the pathogenesis of HS. Both regarding the profiles and the cells, further studies remain to show if these differences are primary events, or secondary to e g chronic inflammation, which is considered a major issue of HS.     

The effects of acute social stress on epidermal Langerhans' cell frequency and expression of cutaneous neuropeptides

Psychological stress is believed to exacerbate inflammatory skin disease but the underlying mechanisms are poorly understood. We investigated the impact of acute social stress--Trier public speaking test--on: epidermal Langerhans' cell (LC) frequency; and cutaneous nerve fiber expression of protein gene product (PGP) 9.5 and calcitonin gene-related peptide (CGRP). Thirty-six healthy volunteers each had a pair of baseline 6 mm biopsies taken from sun-protected buttock skin. A second pair of biopsies was taken from contralateral buttock 4 hours (n=5) or 24 hours (n=15) after the Trier stressor. Controls (n=16) did not perform the Trier and had biopsies 24 hours apart. One of each pair of biopsies (baseline; 4 or 24 hours) was processed for counts of epidermal CD1a(+) LC; the other examined for PGP 9.5 and CGRP expression. We observed a significant (P<0.01) 16.4% reduction in epidermal LC frequency 24 hours post-stressor as compared with baseline; there was no significant change from baseline in non-stressed controls. At 24 hours, PGP 9.5 and CGRP were increased (P=0.025) and reduced (P=0.03), respectively, from baseline in the stressed group compared with controls. These data suggest that acute social stress reduces epidermal LC frequency and modulates cutaneous neuropeptide expression thereby supporting the concept of a "brain-skin" axis.     

Increased innervation of the vulval vestibule in patients with vulvodynia

BACKGROUND: Vulval vestibulitis is a condition characterized by the sudden onset of a painful burning sensation, hyperalgesia, mechanical allodynia, and occasionally pruritus, localized to the region of the vulval vestibulus. It is considered the commonest subset of vulvodynia. Pain precipitated in the absence of nociceptor stimuli might be triggered by previous peripheral nerve injury, or by the release of neuronal mediators, which set off inappropriate impulses in nonmyelinated pain fibres sensitizing the dorsal horn neurones. The pathophysiology of vulval vestibulitis is still unclear. OBJECTIVES: The objective of this study was to evaluate the nerve fibre density and pattern, in specimens of vulval vestibulus, in normal subjects and in patients with vestibulitis, and provide objective diagnostic criteria for this condition. Methods Twelve patients with a history of the vestibulitis type of vulvodynia, and eight normal subjects underwent biopsy of the posterior wall of the vulval vestibule. Quantitative immunohistochemistry was performed, using antisera to the general neuronal marker protein gene product (PGP) 9.5, and to the neuropeptide calcitonin gene-related peptide (CGRP), on 15- microm sections. RESULTS: There was a statistically significant increase of density and number of PGP 9.5 immunoreactive in the papillary dermis of patients with vulvodynia of the vestibulitis type, compared with those of controls. However, the distribution pattern of the innervation showed no significant change. There were no significant differences in CGRP staining between patients and controls. CONCLUSIONS: It is concluded that the increase of PGP 9.5 immunoreactive nerve fibres, in patients with vulvodynia, may be either secondary to nerve sprouting, or may represent neural hyperplasia. Increased innervation may be applied as an objective diagnostic finding in vulval vestibulitis syndrome.     

The occurrence of cutaneous nerve endings and neuropeptides in vitiligo vulgaris: a case-control study

Pioneering studies both in humans and animals have demonstrated an association between the peripheral nervous system and epidermal melanocyte destruction. The presence of certain neuropeptides and neuronal structural markers in peripheral nerve fibres was investigated in involved and uninvolved vitiligo skin and compared with normal healthy skin. A group of 18 vitiligo vulgaris patients and matched healthy volunteers participated in the investigation. The indirect immunofluorescence technique was employed. There was a tendency for a reduction in the number and intensity of low affinity (p75) nerve growth factor receptor immunoreactive (NGFr-IR) basal keratinocytes in involved vitiliginous skin (P<0.06) compared with control skin, while the number of NGFr-IR nerve fibres was significantly increased (P<0.01). The number of calcitonin gene-related peptide (CGRP)-IR nerve fibres in the epidermis and papillary dermis was dramatically increased in involved skin as compared with control skin (P<0.01) and with uninvolved skin (P<0.05). No clear difference could be found in the distribution of vasoactive intestinal polypeptide (VIP)-and neuropeptide tyrosine (NPY)-IR nerve fibres. A different structural appearance of the peripheral nervous system as well as a changed balance of neuropeptides in vitiliginous skin point to a critical role of the nervous system in the pathogenesis of vitiligo. Work was supported by funds from the Medical Faculty of the Karolinska Institute     

五种神经肽在正常头皮中的分布

目的：研究降钙素基因相关肽、P物质、血管活性肠肽、神经肽Y、生长抑素在正常头皮中的分布情况。方法：选用特异性抗体，用免疫组化的方法检测了10例正常头皮标本中五种神经肽的表达情况。结果：研究发现正常头皮的表皮中无这五种神经肽的表达，在真皮中多部位有其阳性纤维分布。结论：正常头皮的真皮中有这五种神经肽的丰富分布。     

Phototherapy reduces the number of epidermal and CGRP-positive dermal nerve fibres

The purpose of this study was to gain an understanding of why phototherapy relieves itching. Skin samples (3 mm punch biopsies) from non-inflamed gluteal skin of 10 patients undergoing phototherapy were compared before and after 20 treatments. All the cutaneous nerve fibres here visualized by antibodies against PGP 9.5, sensory nerve fibres by antibodies against calcitonin gene-related peptide (CGRP) and capsaicin-sensitive primary nociceptive afferents by antibodies against VR1-receptor. Following treatment, the number of PGP 9.5-positive nerve fibres in the epidermis was reduced from 193 +/- 52 to 102 +/- 34 (p < 0.0001) and the number of CGRP-immunoreactive nerve fibres, which occurred only in dermis, was reduced from 28 +/- 15 to 22 +/- 7 (p = 0.04). The VR1-immunoreactive nerve fibres, some of them containing immunoreactivity to CGRP, were not affected. The success of phototherapy in combating itch may at least partly be linked with the reduction in the number of epidermal nerve fibres. The reduction in the number of CGRP-immunoreactive nerve fibres in the dermis may contribute to the beneficial effects of UV irradiation on the inflammatory process.     

Bird's eye view observations of the subepidermal nerve network of normal guinea pig skin

This study was undertaken to visualize the subepidermal nerve networks immunohistochemically. Specimens were obtained from the normal skin of the back, abdomen and nose of seven adult male Hartley guinea pigs, and immersed in 1 M NaCl solution. Dermal sheets were obtained by separating the dermis and epidermis, followed by fixation in Zamboni's fixative. The dermal sheets were sectioned parallel to the separated surface. Using the immunoperoxidase technique and immunofluorescence, the sections were immunostained with primary antibodies to S 100 protein (S100), protein gene product 9.5 (PGP 9.5), neuron-specific enolase (NSE), substance P (SP) and calcitonin gene-related peptide (CGRP). In double-labeled immunofluorescence of PGP 9.5 and SP or CGRP, the sections were viewed under a confocal laser scanning microscope. In skin of the back and abdomen, networks of S100-, PGP 9.5- and NSE-positive fibers were observed, some of which showed a multicentric arrangement. The outermost structures were formed by the thickest fibers which were 5-10 micro m thick, the outer networks consisted of fibers 3-6 micro m thick, and the inner networks consisted of fibers 1-3 micro m thick. From these networks, single fibers approximately 0.5 micro m thick branched out and terminated in free endings. The SP- and the CGRP-positive substances appeared as granules on the PGP 9.5-positive fibers. These results confirm that the dermis has a three-layered sensory nerve plexus, i.e. deep, superficial and subepidermal. In the skin of the nose, however, nerve networks were made up of only thick fibers which were probably situated in the subpapillary dermis.     

A screening of skin changes, with special emphasis on neurochemical marker antibody evaluation, in patients claiming to suffer from "screen dermatitis" as compared to normal healthy controls

Abstract In the present study, facial skin from so-called “screen dermatitis” patients were compared with corresponding material from normal healthy volunteers. The aim of the study was to evaluate possible markers to be used for future double blind or blind provocation investigations. Differences were found for the biological markers calcitonin generelated peptide (CGRP), somatostatin (SOM), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine amide (PHI), neuropeptide tyrosine (NPY). protein S-100 (S-100). neuron-specific enolase (NSR), protein gene product (PGP) 9.5 and phenyl-ethanolamine N-methyltransferase (PNMT). The overall impression in the blind-coded material was such that it turned out easy to blindly separate the two groups from each other. However, no single marker was 100% able to pin-point the difference, although some were quite powerful in doing so (CGRP, SOM. S-100). However, it has to be pointed out that we cannot, based upon the present results, draw any definitive conclusions about the cause of the changes observed. Whether this is due to electric or magnetic fields, a surrounding airborne chemical, humidity, healing, stress factors, or something else, still remains an open question. Blind or double-blind provocations in a controlled environment are necessary to elucidate possible underlying causes for the changes reported in this investigation.     

Plasma concentration of selected neuropeptides in patients suffering from psoriasis

The aim of this study was to evaluate plasma levels of substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) during psoriasis course. METHODS: Seventy-three patients with psoriasis and 32 healthy volunteers were included. Detailed demographic and disease anamnesis was obtained from every patient. The disease severity was assessed using the Psoriasis Area and Severity Index score. Plasma levels of SP, CGRP, VIP and NPY were measured radioimmunologically. RESULTS: Plasma levels of SP and NPY did not significantly differ between patients with psoriasis and controls (median SP: 52.8 and 57.9 pg/ml, respectively; P = 0.32; median NPY: 8.5 and 8.2 pg/ml, respectively; P = 0.67). CGRP plasma concentration was significantly elevated in psoriatic individuals both before (median 43.1 pg/ml) and after treatment (median 45.4 pg/ml), in comparison with healthy donors (median 13.5 pg/ml; P < 0.01 and P = 0.03, respectively). Treatment did not significantly influence plasma CGRP levels (P = 0.3). Median VIP plasma concentration in psoriatics before treatment was significantly higher compared with healthy controls (medians 66.9 and 60.1 pg/ml, respectively; P = 0.04), but the therapy resulted in significant decrease in VIP plasma level (median 19.0 pg/ml; P < 0.001). In psoriatic patients significant correlations were noted between NPY and VIP (R = 0.34; P < 0.01), and VIP and CGRP plasma levels, both before (R = 0.28; P = 0.03) and after the treatment (R = 0.44; P < 0.01). CONCLUSIONS: Based on our results and previous literature data it could be suggested that neuropeptides may be involved in the development of psoriatic lesions.