Skin as a Psychoneuroendocrine Immunology Microcosm: The New Frontier of Low Dose Therapy With Cytokines and Growth Factors in the Systemic Treatment of Chronic Autoimmune Inflammatory Diseases in Dermatology

Abstract

In recent years, the central role of signaling molecules, such as hormones, cytokines and growth factors, has become evident in both physiological and pathological processes; these signaling molecules are the main regulating effectors of whole body biological functions, in accordance with the guiding principle of psychoneuroendocrine immunology (PNEI). Low dose medicine (LDM) represents an innovative medical approach in which the latest evidence in the fields of molecular biology, PNEI and nano-concentration pharmacology are merged. LDM suggests the use of low-doses of activated biological molecules in order to manage PNEI homeostasis, and this approach represents a new opportunity for the development of therapeutic strategies based on immune balancing interventions. Scientific evidence regarding the efficacy and safety of the LDM approach in the treatment of psoriasis vulgaris, and positive preliminary data regarding the oral administration of low dose activated cytokines for vitiligo and atopic dermatitis treatment, support the LDM-based therapeutic approach for many dermatological diseases.Keywords: Psycho-Neuro-Endocrine-Immunology, Low Dose Medicine, Signaling Molecules, Sequential Kinetic Activation, Psoriasis Vulgaris, Dermatologic Diseases ContextIn recent years, a unified vision of the biological functions of the body has been theorized, in accordance with the guiding principles of psychoneuroendocrine immunology (PNEI) (1-4). The PNEI approach represents a paradigm shift from a strictly biomedical view of health and disease to an interdisciplinary view. The main unifying PNEI element is identified in the bi-directional crosstalk (5) between the psychoneuroendocrine systems and the immune system, which is mediated by a complex network of signaling (messenger) molecules (cytokines, hormones, growth factors, neuropeptides) that are the vehicles for the biological information necessary for the complex and efficient regulation of cellular responses to stimuli.The signaling molecules play a decisive role in determining a person's state of health or disease, and it is compelling to consider diseases as expressions of the change in concentrations (both in excess or in defect) of these substances. In order to test the hypothesis that messenger molecules can be used for therapeutic purposes, research in the medical world is increasingly directed toward the study of the messenger molecules, which determine the fate of many pathological conditions in a positive (healing) or negative (disease) way.The multi-system axes, such as the gut-brain-axis and the skin-gut-axis, are controlled and managed by a continuous information exchange driven by cytokines, neuropeptides, neuro-hormones and other signaling molecules, in order to maintain PNEI homeostasis.In summary, altered cross-talk caused by the imbalance between specific signaling molecules is a fundamental requisite for the onset of inflammatory, allergic and autoimmune diseases (6, 7). Preserving and/or restoring the physiological signaling, based on messe...