Stress, atopy and allergy: A re-evaluation from a psychoneuroimmunologic persepective

Abstract

Since the early days of psychosomatic thinking, atopic disease was considered exemplary. In the 70s and 80s numerous reports stated increased anxiety, depression or ill stresscoping in atopics in correlation with enhanced disease activity. Employed patient groups however were small and diverse and controls rare. Therefore, the question remained, whether psychopathological findings in atopics were of pathogenetic relevance or an epiphenomenon of chronic inflammatory disease. Recently, the discussion has been revived and refocused by psychoneuroimmunological findings. We now know that atopic disease is characterized by an imbalance of the classical stress-axis response along the hypothalamus-pituitary-adrenal axis (HPA) and the sympathetic axis (SA). This imbalance can be found shoulder-to-shoulder with enhanced expression of newly emerging neuroendocrine stress mediators such as substance P (SP) and nerve growth factor that form up to a third stress axis (neurotrophin neuropeptide axis: NNA). Together they can alter the inflammatory as well as the neuroendocrine stress-response on several levels. In skin, the immediate inflammatory response to stress involves neuropeptide release and mast cell degranulation, in short neurogenic inflammation. Systemically, antigen-presentation and TH2 cytokine bias are promoted under the influence of cortisol and neuropeptides. Imbalanced stress-responsiveness may therefore be at the core of exacerbated allergic disease and deserves re-evaluation of therapeutic options such as neutralization of SP-signaling by antagonists against its receptor NK1, cortisol treatment as supplementation and relaxation techniques to balance the stress-response.

Keywords: Trk; melanoma; neurotrophins; p75NTR; psoriasis; skin.

Figure 1

Schematic presentation of neuroendocrine stress effects on skin health. Stress dependent activation of the endocrine pathway (HPA) and the sympathetic nervous system (SA) lead to a systemically TH2 bias, playing a role in the onset and/or extending of the allergic component in atopic diseases. The activation of peptidergic innervations directly effects healthy skin homeostasis inducing TH1 cytokines, mast cells degranulation and eosinophilia leading to a neurogenic inflammation (NI). Understanding of the linkage of these three stress axes—how they communicate with each other and how they influence each other opens the research to future targets of possible disease interventions.