title: Paradoxical benefits of psychological stress in inflammatory dermatoses models are glucocorticoid mediated.
abstract: Acute psychological stress (PS) mobilizes metabolic responses that are of immediate benefit to the host, but the current medical paradigm holds that PS exacerbates systemic and cutaneous inflammatory disorders. Although the adverse consequences of PS are usually attributed to neuroimmune mechanisms, PS also stimulates an increase in endogenous glucocorticoids (GCs) that compromises permeability barrier homeostasis, stratum corneum cohesion, wound healing, and epidermal innate immunity in normal skin. Yet, if such PS-induced increases in GC were uniformly harmful, natural selection should have eliminated this component of the stress response. Hence, we hypothesized here instead that stress-induced elevations in endogenous GC could benefit, rather than aggravate, cutaneous function and reduce inflammation in three immunologically diverse mouse models of inflammatory diseases. Indeed, superimposed exogenous (motion-restricted) stress reduced, rather than aggravated inflammation and improved epidermal function in all three models, even normalizing serum IgE levels in the atopic dermatitis model. Elevations in endogenous GC accounted for these apparent benefits, because coadministration of mifepristone prevented stress-induced disease amelioration. Thus, exogenous stress can benefit rather than aggravate cutaneous inflammatory dermatoses through the anti-inflammatory activity of increased endogenous GC.
authors.affiliation: Dermatology Service, Department of Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, California, USA; Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Tzu-Kai
authors.initials: TK
authors.lastname: Lin
authors.affiliation: Dermatology Service, Department of Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Mao-Qiang
authors.initials: MQ
authors.lastname: Man
authors.affiliation: Dermatology Service, Department of Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, California, USA; Department of Dermatology, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain.
authors.forename: Juan-Luis
authors.initials: JL
authors.lastname: Santiago
authors.affiliation: Dermatology Service, Department of Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, California, USA; Department of Dermatology, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Tiffany C
authors.initials: TC
authors.lastname: Scharschmidt
authors.affiliation: Dermatology Service, Department of Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Hupe
authors.affiliation: Department of Dermatology, Hospital del Mar-IMIM, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Martin-Ezquerra
authors.affiliation: Dermatology Service, Department of Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Jong-Kyung
authors.initials: JK
authors.lastname: Youm
authors.affiliation: Dermatology Service, Department of Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Yongjiao
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: ISDIN, Research and Development, Barcelona, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Trullas
authors.affiliation: Medical Service, Department of Veterans Affairs Medical Center, San Francisco, California, USA; Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Feingold
authors.affiliation: Dermatology Service, Department of Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, California, USA; Department of Dermatology, University of California, San Francisco, San Francisco, California, USA. Electronic address: eliasp@derm.ucsf.edu.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Elias
mesh_terms: D000818:Animals; D002463:Cell Membrane Permeability / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D007113:Immunity, Innate / Q000502:physiology; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D008810:Mice, Inbred C57BL; D012867:Skin / Q000378:metabolism* / Q000503:physiopathology; D012871:Skin Diseases / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology*; D013315:Stress, Psychological / Q000378:metabolism* / Q000503:physiopathology; D014945:Wound Healing / Q000502:physiology
chemical_list: D005938:Glucocorticoids; D007073:Immunoglobulin E