Association between Stress and the HPA Axis in the Atopic Dermatitis

Abstract

The hypothalamic-pituitary-adrenal (HPA) axis is one of the body's neuroendocrine networks that responds to psychological stress (PS). In the skin, there exists a peripheral HPA axis similar to the central axis. Glucocorticoids (GCs) are key effector molecules of the HPA axis and are essential for cutaneous homeostasis. Atopic dermatitis (AD) is a condition typically characterized by a chronic relapsing course that often results in PS. HPA dysfunction is present in AD patients by the decreased response of GCs elevation to stress as compared to those unaffected by AD. Nevertheless, in skin, acute PS activates several metabolic responses that are of immediate benefit to the host. During the acute phase of PS, increased endogenous GCs have been shown to provide benefit rather than by aggravating cutaneous inflammatory dermatoses. However, a chronic T helper cell type 2 (Th2) predominant cytokine profile acts as a negative feedback loop to blunt the HPA axis response in AD. In this article, we reviewed the role of CRF, pro-opiomelanocortin (POMC)-derived peptides, GCs of the HPA, and 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in AD, with a discussion of the pathogenetic mechanisms of inflammation and skin barrier functions, including antimicrobial defense, and their association with PS.

Keywords: HPA axis; atopic dermatitis; glucocorticoid; inflammation; psychological stress; skin barrier.

Figure 1

Schematic representation of the Hypothalamic-Pituitary-Adrenal (HPA) axis in the skin. The effects on keratinocytes (left diagram) on AD skin in regards to skin barrier structure and inflammatory response (right diagram). The central HPA axis and the peripheral HPA axis both regulate skin barrier homeostasis and the inflammatory response in the skin. Peripheral nerve endings in the skin are represented in green, whereas dermal capillaries are shown in red. Transepidermal water loss (TEWL) is represented by curled blue lines (right diagram). Corticotrophin-releasing hormone receptor type 1 (CRH-R1); Glucocorticoid receptor (GR); Melanocortin receptor type 1 and 2 (MCR1 and MCR2); 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSD1).

Figure 2

Interactions between the central HPA axis and the cutaneous HPA axis and the effects on the skin barrier and dermatitis. The main hormones, neurotransmitters, and cytokines are highlighted in yellow. Solid arrows represent direct effect of hormones and neurotransmitters related to the HPA axis, whereas dashed lines indicate the influence of psychological stress on other hormones and neurotransmitters that are different from the HPA axis and linked to epidermal homeostasis.