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.


OBJECTIVE
To assess the ability of NPs to influence interleukin (IL)-13 and interferon (IFN)-gamma 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-gamma 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-gamma 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.
Antúnez
C
C
Research Unit for Allergic Diseases, Allergy Service, Carlos Haya Hospital, Málaga, Spain.
Torres
M J
MJ
López
S
S
Rodriguez-Pena
R
R
Blanca
M
M
Mayorga
C
C
Santamaría-Babi
L F
LF
D000293:Adolescent; D000328:Adult; D000954:Antigens, Surface / Q000378:metabolism; D015415:Biomarkers; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D003876:Dermatitis, Atopic / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D055815:Young Adult
D000954:Antigens, Surface; D015415:Biomarkers; D006684:HLA-DR Antigens; D018793:Interleukin-13; D018015:Receptors, Calcitonin Gene-Related Peptide; D007371:Interferon-gamma; D015740:Calcitonin Gene-Related Peptide