title: Further exploring the brain-skin connection: stress worsens dermatitis via substance P-dependent neurogenic inflammation in mice.
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.
authors.affiliation: Psycho-Neuro-Immunology, Center for Internal Medicine and Dermatology, Neuroscience Research Center, Charité-University Medicine, Campus Mitte, Berlin, Germany.
authors.forename: Sanja
authors.initials: S
authors.lastname: Pavlovic
authors.forename: Maria
authors.initials: M
authors.lastname: Daniltchenko
authors.forename: Desmond J
authors.initials: DJ
authors.lastname: Tobin
authors.forename: Evelin
authors.initials: E
authors.lastname: Hagen
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Hunt
authors.forename: Burghard F
authors.initials: BF
authors.lastname: Klapp
authors.forename: Petra C
authors.initials: PC
authors.lastname: Arck
authors.forename: Eva M J
authors.initials: EM
authors.lastname: Peters
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009412:Nerve Fibers / Q000378:metabolism; D020078:Neurogenic Inflammation / Q000276:immunology / Q000503:physiopathology*; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000294:innervation; D013315:Stress, Psychological / Q000276:immunology / Q000503:physiopathology*; D013373:Substance P / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
chemical_list: D016207:Cytokines; D018040:Receptors, Neurokinin-1; D013373:Substance P