title: Mental stress in atopic dermatitis--neuronal plasticity and the cholinergic system are affected in atopic dermatitis and in response to acute experimental mental stress in a randomized controlled pilot study.
abstract: BACKGROUND
  In mouse models for atopic dermatitis (AD) hypothalamus pituitary adrenal axis (HPA) dysfunction and neuropeptide-dependent neurogenic inflammation explain stress-aggravated flares to some extent. Lately, cholinergic signaling has emerged as a link between innate and adaptive immunity as well as stress responses in chronic inflammatory diseases. Here we aim to determine in humans the impact of acute stress on neuro-immune interaction as well as on the non-neuronal cholinergic system (NNCS).
  
  
  METHODS
  Skin biopsies were obtained from 22 individuals (AD patients and matched healthy control subjects) before and after the Trier social stress test (TSST). To assess neuro-immune interaction, nerve fiber (NF)-density, NF-mast cell contacts and mast cell activation were determined by immunohistomorphometry. To evaluate NNCS effects, expression of secreted mammal Ly-6/urokinase-type plasminogen activator receptor-related protein (SLURP) 1 and 2 (endogenous nicotinic acetylcholine receptor ligands) and their main corresponding receptors were assessed by quantitative RT-PCR.
  
  
  RESULTS
  With respect to neuro-immune interaction we found higher numbers of NGF+ dermal NF in lesional compared to non-lesional AD but lower numbers of Gap43+ growing NF at baseline. Mast cell-NF contacts correlated with SCORAD and itch in lesional skin. With respect to the NNCS, nicotinic acetylcholine receptor α7 (α7nAChR) mRNA was significantly lower in lesional AD skin at baseline. After TSST, PGP 9.5+ NF numbers dropped in lesional AD as did their contacts with mast cells. NGF+ NF now correlated with SCORAD and mast cell-NF contacts with itch in non-lesional skin. At the same time, SLURP-2 levels increased in lesional AD skin.
  
  
  CONCLUSIONS
  In humans chronic inflammatory and highly acute psycho-emotional stress interact to modulate cutaneous neuro-immune communication and NNCS marker expression. These findings may have consequences for understanding and treatment of chronic inflammatory diseases in the future.
authors.affiliation: Psychoneuroimmunology Laboratory, Joint appointment a) Center for Internal Medicine and Dermatology, Universitätsmedizin-Charité, Berlin, and b) Department of Psychosomatic Medicine, Justus-Liebig-University, Giessen, Germany.
authors.forename: Eva Milena Johanne
authors.initials: EM
authors.lastname: Peters
authors.affiliation: Psychoneuroimmunology Laboratory, Joint appointment a) Center for Internal Medicine and Dermatology, Universitätsmedizin-Charité, Berlin, and b) Department of Psychosomatic Medicine, Justus-Liebig-University, Giessen, Germany; Department of Dermatology, I. M. Sechenov Moscow Medical University, Moscow, Russia.
authors.forename: Anna
authors.initials: A
authors.lastname: Michenko
authors.affiliation: Institute of Medical Psychology, Justus-Liebig University, Giessen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Kupfer
authors.affiliation: Institute of Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kummer
authors.affiliation: Institute of Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Wiegand
authors.affiliation: Department of Dermatology, University Hospital Giessen, Giessen, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Niemeier
authors.affiliation: Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology, Moscow, Russia.
authors.forename: Nikolay
authors.initials: N
authors.lastname: Potekaev
authors.affiliation: Department of Dermatology, I. M. Sechenov Moscow Medical University, Moscow, Russia.
authors.forename: Andrey
authors.initials: A
authors.lastname: Lvov
authors.affiliation: Department of Psychosomatics and Psychotherapy, Justus-Liebig-University, Giessen, Germany; Department of Dermatology, University Hospital Giessen, Giessen, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Gieler
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis / Q000378:metabolism; D001706:Biopsy; D003876:Dermatitis, Atopic / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008875:Middle Aged; D009412:Nerve Fibers / Q000378:metabolism / Q000473:pathology; D009473:Neuronal Plasticity / Q000276:immunology; D011978:Receptors, Nicotinic / Q000096:biosynthesis / Q000378:metabolism; D013315:Stress, Psychological / Q000150:complications / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D000950:Antigens, Ly; D011978:Receptors, Nicotinic; C048963:SLURP1 protein, human; D014568:Urokinase-Type Plasminogen Activator