Calcitonin gene-related peptide modulates interleukin-13 in circulating cutaneous lymphocyte-associated antigen-positive T cells in patients with atopic dermatitis

Background  Neuropeptides (NPs) may play an important role in the pathogenesis of atopic dermatitis (AD) by regulating immune responses and contributing to the cross-talk between the immune and nervous systems.
Objectives  To assess the ability of NPs to influence interleukin (IL)-13 and interferon (IFN)-γ production and the expression of the activation marker HLA-DR in skin memory T cells [cutaneous lymphocyte-associated antigen (CLA)+ T cells] from patients with AD with severe, chronic lesions and intense pruritus, and from nonatopic controls.
Methods  Cells were cultured in the presence and absence of different NPs, calcitonin gene-related peptide (CGRP), somatostatin (SOM) and substance P (SP). IL-13 and IFN-γ production and HLA-DR expression were measured in both CLA+ and CLA− T-cell subsets by flow cytometry.
Results  CGRP increased IL-13 production in peripheral blood mononuclear cells from patients with AD ( P  <   0·05), with no changes detected in the presence of SOM or SP. These patients with AD had a lower expression of CGRP receptor compared with controls ( P  <   0·05). Memory T cells incubated with CGRP also showed an increase in IL-13 ( P  <   0·05) and HLA-DR ( P  <   0·05) in CLA+ T cells from patients with AD compared with controls, but not in CLA− T cells. Patients with a higher production of IL-13 were those with higher total IgE and percentage of skin area involved. Furthermore, the IL-13/IFN-γ ratio was increased in patients with AD after cells were cultured with CGRP ( P  <   0·05).
Conclusions  Our results suggest an immunomodulatory role of CGRP towards a Th2 pattern in CLA+ T cells, which may contribute to exacerbating clinical symptoms in patients with AD.