Background and objective: In recent years, many reports have suggested an active role of neuropeptides in the pathogenesis of psoriasis. Increased numbers of neuropeptidecontaining 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. Materials and methods: 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 μm 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. Results 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%. Conclusions: 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.
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