vasoactive-intestinal-peptide and Psoriasis

Psoriasis, a chronic inflammatory skin disease, is believed to be exacerbated by stress. The exact mechanism of this phenomenon is not fully understood, however, it has been postulated that different substances released from dermal nerve endings during stress may take part in initiation or modulation of psoriasis. One of the most interesting group of mediators are polypeptides, also named as neuropeptides, that possess vasoactive properties. It was documented that these polypeptides could not only be released from nerve endings, but may also be directly synthesised in the skin and liberated from numerous dermal cells. Moreover, these substances are not only released by different cells, but may activate various cell types showing a wide spectrum of biological actions. Thus, this complex system of interactions seems to be important component of psoriatic pathological reaction. The significant role of these neuromediators has also been postulated in other chronic skin diseases, like palmoplantar pustulosis, atopic and irritant eczema, rosacea, lichen sclerosus, vitiligo, pigmented urticaria or prurigo nodularis. Among different neuropeptides, substance P, calcitonin gene-related peptide, vasoactive intestinal peptide (VIP) and neuropeptide Y have been mostly studied in psoriasis.

Topics: Calcitonin Gene-Related Peptide; Humans; Nerve Growth Factor; Neuropeptide Y; Psoriasis; Substance P; Vasoactive Intestinal Peptide

The pathogenesis of psoriasis is incompletely understood but cutaneous neurogenic inflammation is probably involved. This involvement is suggested by a number of clinical and histological observations. Reports about the distribution of cutaneous nerves and the quantification of nerve growth factor and neuropeptides, including calcitonin gene-related peptide and vasoactive intestinal peptide, in lesional and nonlesional psoriatic skin suggest that sensory neuropeptides contribute to the development of psoriasis. This review summarizes what is known about the role of neurogenic markers in psoriasis.

Topics: Calcitonin Gene-Related Peptide; Humans; Nerve Growth Factors; Neuropeptides; Psoriasis; Substance P; Vasoactive Intestinal Peptide

Peptide T, the HIV envelope-derived fragment Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr, has already been used to successfully treat psoriatic patients without major side-effects. The underlying reason for the positive effect is, however, at present unknown. In the following minireview, we summarize today's knowledge regarding peptide T's interaction with other chemical messenger molecules, such as somatostatin, vasoactive intestinal polypeptide (VIP) and epidermal growth factor (EGF), within the human skin, and, finally, speculate about their relationship to each other. In summary, we believe that the clearance effect of peptide T on psoriasis will open up new avenues with regard to the concept of the pathogenesis of as well as the clinical attendance to this disease.

Topics: Amino Acid Sequence; Humans; Molecular Sequence Data; Peptide T; Psoriasis; Vasoactive Intestinal Peptide

To observe the efficacy of Zhuhuang Granule No. 2 (ZHG2) in treating psoriasis with Liver-Qi stagnancy.. Sixty-seven patients were randomly divided into two groups, the 33 patients in the control group were treated with composite indigo capsule and the 34 in the treated group treated with ZHG2, and the clinical effect, changes of main symptoms and local skin lesion after treatment were evaluated. Meanwhile, the plasma levels of substance P (SP) and vasoactive intestinal peptide (VIP) in 15 patients and 13 healthy subjects were measured using radioimmunoassay (RIA).. The total effective rate in the treated group and the control group was 97.1% and 78.8% respectively with significant difference, P < 0.05. ZHG2 showed a significant effect in reducing plasma level of SP and VIP in patients of psoriasis with Liver-Qi stagnancy.. The effect of ZHG2 in treating psoriasis patients with Liver-Qi stagnancy is satisfactory, and worth further studying.

Topics: Adult; Diagnosis, Differential; Drugs, Chinese Herbal; Female; Humans; Male; Medicine, Chinese Traditional; Middle Aged; Phytotherapy; Psoriasis; Substance P; Vasoactive Intestinal Peptide

Clinical findings suggest that an etiological factor of skin psoriasis (SPs) is of nervous origin. Vasoactive intestinal peptide (VIP) is the most probable candidate for such a factor since VIP is the only neurotransmitter the extracellular level of which increases during SPs exacerbation and decreases in remission. VIP released from skin nerves induces keratinocyte hyperproliferation, angiogenesis, vasodilation, and other SPs-associated cutaneous pathological processes. These can go on over a prolonged period since (1) once released, VIP induces its own further secretion; (2) VIP induces release of interleukin-6 (IL6) that evokes both its own further release and release of VIP. Thereby, a vicious circle-type mechanism perpetuating and amplifying VIP secretion can function in the focuses of psoriatic damage. The mechanism described operates still more intensively under the effects of parathyroid hormone, aldosterone, and enkephalin, the blood levels of which are elevated in patients with SPs. The above explains such features of SPs as its association with human immunodeficiency virus infection, mental stress, alcohol consumption, smoking, and dependence of SPs on skin pigmentation.

Topics: Humans; Psoriasis; Skin; Vasoactive Intestinal Peptide

Overexpression of vascular endothelial growth factor (VEGF) in epidermal lesions of psoriasis is well documented; however, its underlying mechanisms are largely unknown. We have recently demonstrated that vasoactive intestinal peptide (VIP) induces the production of cytokines such as interleukin-6 and stem cell factor from keratinocytes, thereby contributing to the development of inflammatory dermatoses such as psoriasis.. In this study, we attempted to determine whether VIP could increase the production of VEGF in human keratinocytes.. We examined the expression of VEGF using reverse transcription-polymerase chain reaction, immunocytochemistry, enzyme-linked immunosorbent assay and immunoblotting in normal human epidermal keratinocytes and human epidermal keratinocyte cell line DJM-1 cultured in the absence or presence of VIP and/or inflammatory cytokines.. We demonstrate that human keratinocytes produced VEGF in a steady state at both mRNA and protein levels. VIP significantly upregulated the production of VEGF in keratinocytes in a dose- and time-dependent manner. The VIP-mediated production of VEGF was further enhanced by inflammatory cytokines such as interferon-gamma, tumour necrosis factor-alpha and interleukin-4, with maximum enhancement being observed with the combination of VIP and interferon-gamma.. VIP and other cytokines from nerve endings, mast cells and local inflammatory cells are capable of enhancing VEGF production from epidermal keratinocytes, which may underlie excessive angiogenesis and vasodilation in skin lesions of psoriasis.

Topics: Blotting, Western; Cell Line; Cytokines; Enzyme-Linked Immunosorbent Assay; Epidermal Cells; Humans; Immunohistochemistry; Keratinocytes; Psoriasis; Reverse Transcriptase Polymerase Chain Reaction; Vascular Endothelial Growth Factor A; Vasoactive Intestinal Peptide

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.. 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.. 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).. Based on our results and previous literature data it could be suggested that neuropeptides may be involved in the development of psoriatic lesions.

Topics: Adult; Aged; Aged, 80 and over; Calcitonin Gene-Related Peptide; Case-Control Studies; Female; Humans; Inflammation Mediators; Male; Middle Aged; Neuropeptide Y; Neuropeptides; Psoriasis; Stress, Physiological; Substance P; Vasoactive Intestinal Peptide

Topics: Adult; Aged; Case-Control Studies; Cell Line; Cells, Cultured; Dose-Response Relationship, Drug; Female; Fibroblasts; Humans; Male; Mast Cells; Middle Aged; Nitric Oxide; Psoriasis; Substance P; Vasoactive Intestinal Peptide

In recent years, many reports have suggested an active role of neuropeptides in the pathogenesis of psoriasis. Increased numbers of neuropeptide-containing nerves positive for substance P (SP), vasoactive intestinal polypeptide (VIP), and calcium gene-related peptide (CGRP) have been reported in psoriatic tissue. As psoriatic epidermis has a larger mass/volume, however, it is expected to have more nerves and a higher number of neuropeptergic fibers. Therefore, instead of demonstrating a larger number of neuropeptergic fibers, a more significant study is to investigate whether the neuropeptergic fibers are denser in psoriatic tissue. In this study, we applied a double labeled immunofluorescence technique. This method allows the identification of the total number of nerve fibers and the number of nerves positive for specific neuropeptides.. We obtained biopsies from nine lesional and seven non-lesional psoriatic skins and six normal controls. Biopsies were snap frozen and then cut into 14 microm cryosections. The tissues were first treated with anti-microtubule associated protein (MAP)2 antibody to stain the nerves. This was followed by a second set of stainings for SP, VIP, and CGRP. Primary antibodies were used in dilutions of 1:200 for anti-MAP2, 1:200 for anti-SP, 1:800 for anti-VIP, and 1:400 for anti-CGRP.. We found that the percentage of SP-positive fibers was twofold greater and the percentage of CGRP-positive fibers was 2.5 times greater in the psoriatic epidermis than in the epidermis of normal skin. Psoriatic epidermis had 30.1 +/- 3.9% SP-positive nerve fibers compared with 15.7 +/- 3.7% in the normal control. The corresponding values for CGRP-positive nerve fibers were 30.1 +/- 3.9% and 12.0 +/- 4.2%.. The results of our study suggest that SP- and CGRP-containing neuropeptide nerve fibers are more dense in the psoriatic epidermis. Both SP and CGRP are chemotactic to neutrophils and mitogenic to keratinocytes and endothelial cells. In addition, SP activates T lymphocytes and induces adhesion molecules on the endothelial cells. Our observations suggest that neuropeptides may play a significant role in the inflammatory and proliferative process of psoriasis.

Topics: Calcitonin Gene-Related Peptide; Fluorescent Antibody Technique, Indirect; Humans; Microtubule-Associated Proteins; Nerve Fibers; Neurons, Afferent; Psoriasis; Skin; Substance P; Vasoactive Intestinal Peptide

In order to evaluate more fully the role of neuropeptides in the pathogenesis of psoriasis, skin biopsies were obtained from 36 patients with psoriasis to identify substance P (SP), vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP). Lesional and nonlesional skin was examined from these biopsies and the results compared with those from biopsies taken from patients with a variety of other inflammatory dermatoses, including lichen planus, lichen simplex chronicus, spongiotic dermatitis, and seborrheic dermatitis. Also studied was a series of nine biopsies taken from patients with no known skin disorders. We found an increase in the number of SP-positive nerve fibers within the epidermis in biopsies from lesional skin of psoriasis patients (8.4 nerves per 3-mm biopsy) compared with nonlesional psoriatic skin (2.6 nerves per 3-mm biopsy) and normal skin (2.0 nerves per 3 mm biopsy). Other inflammatory disorders also demonstrated fewer SP-positive nerves than lesional psoriatic skin; lichen planus (0 nerves per 3 mm biopsy) and lichen simplex chronicus (1.3 nerves per 3 mm biopsy). The difference in SP-positive nerve expression between lesional psoriatic skin and the group comprising nonlesional skin, normal skin, lichen planus, and lichen simplex chronicus attained statistical significance (P < 0.013). SP-positive intraepidermal nerve fibers in lesional psoriatic specimens were fewer than in spongiotic dermatitis (17.4 nerves per 3 mm biopsy). There was no significant difference in numbers of VIP- or CGRP-immunopositive intraepidermal nerve fibers between psoriatic skin and the group comprising all other material tested. However, in five patients with psoriasis, there was a marked increase in the expression of intraepidermal CGRP (up to 10.7 nerves per 3-mm biopsy) and VIP (up to 8.3 nerves per 3-mm biopsy) which was not observed in control groups. These findings suggest that neuropeptides SP, CGRP, and VIP play a role in the pathogenesis of psoriasis.

Topics: Adult; Aged; Calcitonin Gene-Related Peptide; Epidermis; Female; Humans; Male; Middle Aged; Nerve Fibers; Psoriasis; Substance P; Vasoactive Intestinal Peptide

To study the elements of neurogenic inflammation in psoriatic skin, morphological contacts were examined between mast cells and sensory nerves containing the neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP) or vasoactive intestinal polypeptide (VIP). Because mast cells in psoriatic lesions appear in great numbers at the basement membrane (BM) zone, neuropeptide-mast cell contacts with the BM were also counted. A double stain for active mast cell tryptase and the neuropeptides was applied and the contacts were quantitated morphometrically. Sensory nerve-mast cell contacts were also studied three-dimensionally with a confocal laser scanning microscope. Increases in the contact values of SP and CGRP with mast cells, as well as with the BM, were obtained in developing (1-3 weeks) lesions when compared with their non-lesional controls. This increase reached statistical significance in mature lesions. In contrast, the corresponding contact values for VIP were decreased. By confocal microscopy, a close association between mast cells and sensory nerves was observed in the lesional dermis. Since tryptase is known to degrade CGRP but not SP, neurogenic stimuli, mainly via SP, can result in degranulation of mast cells, which release substances to enhance inflammation. At the BM zone in psoriatic lesions, the numerous mast cells loaded with tryptase can promote degradation of BM components and allow entry of various mediators to interact with keratinocytes.

Topics: Adult; Aged; Basement Membrane; Calcitonin Gene-Related Peptide; Female; Histocytochemistry; Humans; Male; Mast Cells; Microscopy, Confocal; Microscopy, Fluorescence; Middle Aged; Peripheral Nerves; Psoriasis; Substance P; Vasoactive Intestinal Peptide

The distribution of the neuropeptides substance P (SP), vasoactive intestinal polypeptide (VIP) and calcitonin gene related peptide (CGRP) was studied immunohistochemically in psoriatic skin during the Koebner response (6 h, 2 days, 7 days, 14 days, 21 days), and in mature psoriatic plaques, of 37 psoriatic patients. The morphological association of sensory nerves, SP and VIP with papillary mast cells was also monitored. The nerves containing SP, VIP or CGRP were very scanty in control skin, and in non-lesional and Koebner-negative psoriatic skin. The first psoriatic lesions were seen 7 days after tape stripping the symptomless psoriatic skin. SP- and VIP-containing nerves were slightly increased in Koebner-positive specimens, but the increase was very prominent in dermal papillae of mature psoriatic plaques. In the plaques, nerve-mast cell contacts were significantly increased (p < 0.001) compared with non-lesional psoriatic skin. Only SP-positive fibres were detected in the epidermis and in contact with papillary mast cells. VIP was mainly located around capillaries where SP was also found. No change was noted in CGRP-positive fibres between lesional and non-lesional specimens. The appearance of SP and VIP in the capillary walls is morphological evidence for their function as vasodilators in psoriatic lesion. A slight increase in SP- and VIP-positive fibres in Koebner-positive specimens suggests that these neuropeptides may participate in the inflammatory reaction at an early stage. Their prominence in mature psoriatic plaques in turn indicates a role for them in the maintenance of psoriatic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Calcitonin Gene-Related Peptide; Cell Adhesion; Female; Humans; Immunohistochemistry; Male; Mast Cells; Middle Aged; Neurons, Afferent; Neuropeptides; Psoriasis; Substance P; Vasoactive Intestinal Peptide

An involvement of neurogenic components in the pathogenesis of psoriatic lesions has been suggested and neuropeptides are thought to play a modulatory role in cutaneous inflammation. In this study, we evaluated the immunoreactivity of the neuropeptides vasoactive intestinal polypeptide (VIP) and substance P (SP) in the skin of patients with chronic plaque psoriasis, by immunohistochemistry and radioimmunoassay. No differences were observed, by immunohistochemistry, in the expression and localization of VIP and SP between psoriatic and normal skin. Using the radioimmunologic technique on whole skin homogenates, VIP levels were significantly increased in psoriatic lesions as compared to normal skin. By contrast, SP levels were significantly lower in lesional and non-lesional psoriatic skin than in normal skin. In addition, we examined the effect of VIP and SP on the proliferation of cultured normal human keratinocytes. VIP (1-28) (1 nM-1 microM) as well as VIP fragments (10-28) (1 nM-1 microM) and (22-28) (1 nM-1 microM) stimulated the proliferation of keratinocytes in a dose-dependent manner, whereas the VIP fragment (1-12) (1 nM-1 microM) was ineffective. The VIP antagonist (N-Ac-Tyr1, D-Phe2)-GRF (1-29)-NH2 (0.1 microM) significantly inhibited the VIP effect on keratinocytes. On the other hand, SP (0.1 microM) not only failed to stimulate keratinocyte growth, but also blocked the VIP-induced stimulation of these cells. The imbalance of cutaneous VIP and SP and their disparate effects on the proliferation of normal human keratinocytes in culture would suggest that these peptides are involved in the pathogenesis of psoriasis and may exert different modulatory activities in the mechanisms underlying the psoriatic lesion.

Topics: Cell Division; Cells, Cultured; Humans; Immunohistochemistry; Keratinocytes; Psoriasis; Radioimmunoassay; Substance P; Vasoactive Intestinal Peptide

The neuropeptides vasoactive intestinal polypeptide (VIP), substance P and somatostatin were studied in skin biopsies from patients with eczema, psoriasis and axillary hyperhidrosis. VIP concentrations were elevated in skin affected by eczema and psoriasis, whereas substance P and somatostatin levels did not differ from controls. There was a higher concentration of VIP, but not of substance P or somatostatin, in normal axillary skin when compared to adjacent trunk skin, with abundant VIP-containing fibres surrounding eccrine sweat glands. The VIP concentration was unchanged in skin affected by axillary hyperhidrosis. VIP may increase local blood flow in eczema and psoriasis, but does not appear to play a role in axillary hyperhidrosis.

Topics: Adult; Axilla; Dermatitis, Atopic; Humans; Hyperhidrosis; Middle Aged; Psoriasis; Regional Blood Flow; Skin; Somatostatin; Substance P; Vasoactive Intestinal Peptide

Epidermal cells from psoriatic lesions demonstrate a very low cAMP response to beta-adrenergic stimuli. We have shown that a similar abnormality occurs in dermal fibroblasts from affected areas of skin. The cells, after 5-12 passages in tissue culture, had a much reduced response to 10(-8) M and 10(-6) M isoproterenol when compared with fibroblasts from control subjects. The abnormality was not abolished by the addition of the phosphodiesterase inhibitor, 3-isobutyl-I-methylxanthine. Other putative agonists tested were vasoactive intestinal peptide and peptide histidine methionine. Neither of these had an effect on dermal fibroblasts from either normal controls or from lesions of psoriasis.

Topics: 1-Methyl-3-isobutylxanthine; Adult; Cells, Cultured; Cyclic AMP; Female; Fibroblasts; Humans; Isoproterenol; Male; Peptide PHI; Psoriasis; Skin; Stimulation, Chemical; Vasoactive Intestinal Peptide

Immunoreactivity for phenylethanolamine N-methyltransferase (PNMT), the enzyme involved in the conversion of norepinephrine to epinephrine, was present in the basal epidermis and upper dermis in 16 patients with psoriasis. The amount of immunoreactivity was increased tenfold in involved compared to uninvolved skin as characterized by computer-assisted image analysis. In skin from healthy volunteers no immunoreactivity could be found. In our subjects, no immunoreactivity was observed for the other catecholamine synthesizing enzymes (tyrosine hydroxylase; dopa-decarboxylase; dopamine-beta-hydroxylase), apart from single tyrosine hydroxylase positive adrenergic vascular nerves. Furthermore, in psoriasis, the immunoreactivity pattern of the peptides somatostatin, substance P, vasoactive intestinal polypeptide and bombesin was in agreement with skin from healthy volunteers.

Topics: Adult; Bombesin; Dopa Decarboxylase; Dopamine beta-Hydroxylase; Female; Humans; Male; Phenylethanolamine N-Methyltransferase; Psoriasis; Skin; Somatostatin; Substance P; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide