Neurotensin serum levels and skin gene expression are increased in atopic dermatitis

Background Neurotensin (NT) participates in immune responses, but the mechanisms are not known. We have previously shown that NT augments the ability of corticotropin-releasing hormone (CRH) to increase mast-cell-dependent vascular permeability in rodents. We also showed that NT stimulates human mastcell release of vascular endothelial growth factor, and that CRH is increased in the serum of patients with atopic dermatitis (AD), an inflammatory skin condition involving mast cells. Objectives To measure serum levels of NT, and lesional skin expression of NT and the main NT receptor (NTR-1) in AD, and to compare it with skin expression in chronic urticaria (CU) and urticaria pigmentosa (UP). Methods Serum NT was measured with a Milliplex microbead array. Skin NT and NTR-1 gene expression was determined with quantitative polymerase chain reaction. Immunohistochemistry was performed using a mouse monoclonal antibody for NT, and a rabbit polyclonal antibody for NTR-1. Mast cells were counterstained with Leder dye. Results Neurotensin is significantly elevated in the serum of patients with AD compared with healthy controls (P = 0.0001). NT gene expression is also significantly increased in lesional skin of patients with AD compared with controls (P = 0.0194). Moreover, immunohistochemistry of AD lesions shows NT > NTR-1 staining of perivascular cells, many of which are identified as mast cells after staining with Leder dye. There was no statistically significant difference in NT and NTR-1 lesional skin gene expression in patients with either CU or UP. Conclusions These results suggest that interactions between NT and mast cells may occur and contribute to AD pathogenesis. What's already known about this topic? Atopic dermatitis worsens with stress, and its pathogenesis involves mast cells and neuropeptides. What does this study add? Neurotensin is increased in the serum and skin under stress. It activates mast cells and stimulates release of inflammatory molecules. Neurotensin is increased in lesional skin of patients with atopic dermatitis but not patients with chronic urticaria or urticaria pigmentosa.