Psychological Stress and the Cutaneous Immune Response: Roles of the HPA Axis and the Sympathetic Nervous System in Atopic Dermatitis and Psoriasis

Abstract

Psychological stress, an evolutionary adaptation to the fight-or-flight response, triggers a number of physiological responses that can be deleterious under some circumstances. Stress signals activate the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system. Elements derived from those systems (e.g., cortisol, catecholamines and neuropeptides) can impact the immune system and possible disease states. Skin provides a first line of defense against many environmental insults. A number of investigations have indicated that the skin is especially sensitive to psychological stress, and experimental evidence shows that the cutaneous innate and adaptive immune systems are affected by stressors. For example, psychological stress has been shown to reduce recovery time of the stratum corneum barrier after its removal (innate immunity) and alters antigen presentation by epidermal Langerhans cells (adaptive immunity). Moreover, psychological stress may trigger or exacerbate immune mediated dermatological disorders. Understanding how the activity of the psyche-nervous -immune system axis impinges on skin diseases may facilitate coordinated treatment strategies between dermatologists and psychiatrists. Herein, we will review the roles of the HPA axis and the sympathetic nervous system on the cutaneous immune response. We will selectively highlight how the interplay between psychological stress and the immune system affects atopic dermatitis and psoriasis.

Figure 1

A schematic representation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous interaction with the cutaneous immune system. Stress signals induce release of hormones, including corticotropin-releasing hormone (CRH) from the paraventricular nucleus (PVN) of the hypothalamus. CRH induces adrenocorticotropic hormone (ACTH) release from the anterior pituitary [20]. In turn, ACTH regulates glucocorticoid secretion from the adrenal cortex [22]. Cortisol has several functions including negative feedback of the hypothalamus and anterior pituitary and induces epinephrine and norepinephrine from the adrenal medulla [23]. Glucocorticoids, such as cortisol, as well as epinephrine and norepinephrine may enhance cutaneous immune responses at low concentrations and suppress immune responses at high concentrations [5, 28]. Stress signals also stimulate the locus coeruleus (LC) norepinephrine cells (NE) of the sympathetic nervous system [18]. Neuropeptide products of the sympathetic response (substance P (SP), calcitonin gene-related peptide (CGRP), and cutaneous nerve growth factor (NGF)) have been shown to be proinflammatory and anti-inflammatory dependent on the immune cell type [–34]. There also exists a positive, reverberatory feedback loop between the HPA axis and LC-NE [18, 21]. Results show that HPA and sympathetic stress responses both modify the cutaneous immune response.