Neuropeptides in the skin of patients with atopic dermatitis.
There is increasing evidence that neuropeptides may be involved in the pathogenesis of atopic dermatitis (AD). This study examines whether neuropeptide distribution in the skin of patients with AD differs from normal controls. The distribution and density of several neuropeptides were examined in lesional and non-lesional skin of AD patients (n = 5) and in normal controls (n = 4) using indirect immunofluorescence and image analysis. Cholinergic innervation was studied using cholinesterase histochemistry. Staining with the general neuronal marker protein gene product 9 x 5 showed a subepidermal network of nerves with fibres penetrating the epidermis, and nerves around blood vessels, sweat glands and hair follicles. Image analysis of nerves around sweat glands showed a significantly higher nerve density in non-lesional compared with both normal controls and lesional skin (P < 0.05); lesional compared with control skin showed no significant difference. In the epidermis the density of nerves was not significantly greater in non-lesional compared with lesional skin and controls. Calcitonin gene-related peptide immunoreactivity was similar in all subjects except in three of the AD patients, where more nerves appeared to penetrate the epidermis. Substance P immunoreactivity in the papillary dermis was seen in all AD patients but no controls. Vasoactive intestinal polypeptide and neuropeptide Y staining were similar in all groups. Acetylcholinesterase-positive nerves were found around sweat glands in all subjects, the staining being greatest in non-lesional and least in lesional skin. Occasional nerves were seen in the papillary dermis in lesional skin of two out of the four patients. We have demonstrated quantitative differences in nerve growth in clinically normal skin of AD patients, and altered cutaneous neuropeptide expression in these patients which may contribute to the pathogenesis of AD. The cause of atopic dermatitis (AD) has not been fully established but it is believed that there is a complex interaction between genetic susceptibility, precipitating environmental factors and disordered immune responsiveness. There is increasing evidence that neuropeptides may be involved in the pathogenesis of AD. Exacerbations of the disease can be provoked by stress, scratching and sweating which may be the result of neurogenic inflammation. One of the first features of an exacerbation is flushing of the affected skin and pruritus. Several neuropeptides that have been identified in human skin are potent inducers of vasodilation and may induce pruritus. Substance P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) all cause vasodilation when injected intradermally, and SP and CGRP have been shown to be mediators of the weal and flare reaction. Spantide, a competitive antagonist of SP, has been shown to inhibit immediate and delayed-type hypersensitivity reactions. Part of these responses may be due to release of histamine and indeed elevated concentrations of histamine have been found in vivo in the skin and plasma of patients with AD. In this study the distribution and density of several neuropeptides were examined in lesional and nonlesional skin of AD patients and in normal controls using indirect immunofluorescence and image analysis. Cholinergic innervation was studied using cholinesterase histochemistry. Because many afferent fibres do not express CGRP or SP, the general neuronal marker protein gene product (PGP 9 x 5) was used to assess the overall nerve supply to the skin.
Ostlere
L S
LS
Department of Dermatology, The Royal Free Hospital and School of Medicine, Hampstead, London, UK.
Cowen
T
T
Rustin
M H
MH
D000110:Acetylcholinesterase / Q000032:analysis / Q000378:metabolism; D000328:Adult; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000378:metabolism*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D009478:Neuropeptide Y / Q000032:analysis / Q000378:metabolism; D009479:Neuropeptides / Q000032:analysis / Q000378:metabolism*; D012867:Skin / Q000737:chemistry / Q000294:innervation / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000032:analysis / Q000378:metabolism
D009478:Neuropeptide Y; D009479:Neuropeptides; D014660:Vasoactive Intestinal Peptide; D000110:Acetylcholinesterase; D015740:Calcitonin Gene-Related Peptide