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
Rationale 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
