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Paradoxical benefits of psychological stress in inflammatory dermatoses models are glucocorticoid mediated.

Lin TK, Man MQ, Santiago JL, Scharschmidt TC, Hupe M, Martin-Ezquerra G, Youm JK, Zhai Y, Trullas C, Feingold KR, Elias PM - J. Invest. Dermatol. (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: 1] Dermatology Service, Department of Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, California, USA [2] Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan [3] Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

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.

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Related in: MedlinePlus

Stress reduces epidermal hyperplasia and inflammation in acute allergic contact dermatitis (ACD) mice. (a–c) Representative hematoxylin and eosin sections of normal or ACD mice, with or without superimposed stress. (d–f) Proliferating cell nuclear antigen (PCNA) immunostaining in parallel sections (see a–c). (g) Quantification of epidermal hyperplasia (thickness) of nucleated cell layers, PCNA+cells (PNA+cells/unit length of basal layer), and inflammatory cell density/mm2. Bar=20 μm.
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fig2: Stress reduces epidermal hyperplasia and inflammation in acute allergic contact dermatitis (ACD) mice. (a–c) Representative hematoxylin and eosin sections of normal or ACD mice, with or without superimposed stress. (d–f) Proliferating cell nuclear antigen (PCNA) immunostaining in parallel sections (see a–c). (g) Quantification of epidermal hyperplasia (thickness) of nucleated cell layers, PCNA+cells (PNA+cells/unit length of basal layer), and inflammatory cell density/mm2. Bar=20 μm.

Mentions: We next evaluated the impact of exogenous stress in an ACD mouse model in which either the hapten, Ox, or vehicle alone was applied once to opposing ears of previously sensitized mice, under either stressed or nonstressed conditions. Exogenous stress again markedly reduced visible erythema and scale in Ox-challenged ears (Figure 1c), changes that were paralleled by significant reductions in ear thickness (Figure 1d) and inflammatory cell infiltrations (Figures 1e and 2g), as well as histologic evidence of a marked reduction in dermal inflammation (Figure 2a–c and Supplementary Figure 3C and D online). The stress-induced reductions in epidermal hyperplasia were mirrored by a normalization of epidermal hyperplasia and epidermal thickness, further quantified as a decreased density of proliferating cell nuclear antigen (PCNA)-positive basal cells (Figure 2d–g). Together, these results show that the imposition of exogenous stress displays potent anti-inflammatory activity in a mouse model of ACD.


Paradoxical benefits of psychological stress in inflammatory dermatoses models are glucocorticoid mediated.

Lin TK, Man MQ, Santiago JL, Scharschmidt TC, Hupe M, Martin-Ezquerra G, Youm JK, Zhai Y, Trullas C, Feingold KR, Elias PM - J. Invest. Dermatol. (2014)

Stress reduces epidermal hyperplasia and inflammation in acute allergic contact dermatitis (ACD) mice. (a–c) Representative hematoxylin and eosin sections of normal or ACD mice, with or without superimposed stress. (d–f) Proliferating cell nuclear antigen (PCNA) immunostaining in parallel sections (see a–c). (g) Quantification of epidermal hyperplasia (thickness) of nucleated cell layers, PCNA+cells (PNA+cells/unit length of basal layer), and inflammatory cell density/mm2. Bar=20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4227540&req=5

fig2: Stress reduces epidermal hyperplasia and inflammation in acute allergic contact dermatitis (ACD) mice. (a–c) Representative hematoxylin and eosin sections of normal or ACD mice, with or without superimposed stress. (d–f) Proliferating cell nuclear antigen (PCNA) immunostaining in parallel sections (see a–c). (g) Quantification of epidermal hyperplasia (thickness) of nucleated cell layers, PCNA+cells (PNA+cells/unit length of basal layer), and inflammatory cell density/mm2. Bar=20 μm.
Mentions: We next evaluated the impact of exogenous stress in an ACD mouse model in which either the hapten, Ox, or vehicle alone was applied once to opposing ears of previously sensitized mice, under either stressed or nonstressed conditions. Exogenous stress again markedly reduced visible erythema and scale in Ox-challenged ears (Figure 1c), changes that were paralleled by significant reductions in ear thickness (Figure 1d) and inflammatory cell infiltrations (Figures 1e and 2g), as well as histologic evidence of a marked reduction in dermal inflammation (Figure 2a–c and Supplementary Figure 3C and D online). The stress-induced reductions in epidermal hyperplasia were mirrored by a normalization of epidermal hyperplasia and epidermal thickness, further quantified as a decreased density of proliferating cell nuclear antigen (PCNA)-positive basal cells (Figure 2d–g). Together, these results show that the imposition of exogenous stress displays potent anti-inflammatory activity in a mouse model of ACD.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: 1] Dermatology Service, Department of Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, California, USA [2] Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan [3] Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

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.

Show MeSH
Related in: MedlinePlus