1. ¹Psycho-Neuro-Immunology, Center for Internal Medicine and Dermatology, Neuroscience Research Center, Charité—University Medicine, Campus Mitte, Berlin, Germany
2. ²Department of Biomedical Sciences, Bradford University, Bradford, UK
3. ³Psycho-Neuro-Immunology, Center for Internal Medicine and Dermatology, Biomedical Research Center, Charité—University Medicine, Campus Virchow, Berlin, Germany
4. ⁴Department of Anatomy and Developmental Biology, University College London, London, UK
5. ⁵Center for Internal Medicine and Dermatology, Department of Psychosomatic Medicine, Charité—University Medicine, Campus Mitte, Berlin, Germany

Correspondence: Dr Eva M.J. Peters, Psychoneuroimmunology, Biomedical Research Center, Room Number 2.0549, Universitätsmedizin Charité, Campus Virchow Klinikum, Humboldtuniversität Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany. E-mails: eva.peters@charite.de or frl_peters@yahoo.com

Received 13 March 2007; Revised 18 June 2007; Accepted 11 July 2007; Published online 4 October 2007.

Abstract

A neurogenic component in atopy and allergy is evident and potentially of great pathogenic relevance. Stress was recently shown to activate elements of this component and is vividly discussed as a cause of exacerbation. However, to date, scientific proof of stress-induced neuronal plasticity and neuro-immune interaction in atopy or allergy remains lacking. Here we show early evidence that exposure to sound stress and atopic dermatitis-like allergic dermatitis (AD) equipotently raise the number of cutaneous nerve fibers containing the prototypic stress neuropeptide substance P (SP) in mice. Stress increases AD readout parameters by at least 30% (eosinophil infiltration, vascular cell adhesion molecule-positive blood vessels, epidermal thickness). This dramatic pathologic exacerbation is associated with increased neurogenic inflammation (degranulated mast cells; interstitial neuropeptidergic dense core granules, mast cell apoptosis, endothelial gaping). Key features of AD exacerbation could not be induced in mice lacking the neurokinin-1 SP receptor (NK₁). Interestingly, stress had no significant additional effect on CD4+ cell number, but shifted the cytokine profile toward TH2 in skin. Thus, we conclude that stress primarily exacerbates AD via SP-dependent cutaneous neurogenic inflammation and subsequent local cytokine shifting and should be considered as a therapeutic target, while it offers a convincing pathogenic explanation to affected patients and their frustrated physicians alike.