**Neuropeptides in skin immunity**

It was reported that neuropeptides display antimicrobial activities, linking together nervous and immune system (Radek & Gallo, 2007; Sternberg, 2006). Both systems can influence each other: brain and peripheral nervous system directly influence the activity of innate and adaptive immune system. Immune system can relay signals to the nervous system *via* the production of growth factors and cytokines. For example, stress can induce alterations in the immune response (Webster et al. 2002), or can be elicited by infection or injury with release of neuropeptides (Brogden et al., 2005).

Exchange between both systems can occur at systemic, as well as at regional or local levels (Sternberg, 2006). The first, global level gathers sympathetic nervous system, the hypothalamic-pituitary-adrenal axis and circulating AMPs. The second, local level, is composed of nervous endings, neuropeptide-releasing cells and receptors-exhibiting cells.

At the skin level, important structures, such as Merkel cells (Lucarz & Brand, 2007) localized at the basement membrane, separating epidermis from dermis, are neuropeptide-producing cells, cutaneous nervous cells and target cells. Merkel cells have characteristics of both epidermal and neuroendocrine cells. They are connected to nervous system with terminal sensory synapses and dense-core granules contain CGRP (Calcitonin Gene Related Peptide), VIP (VasoIntestinal Peptide), and CgA (Chromogranin A)-derived peptides (Hartschuh et al., 1989a; Hartschuh et al., 1989b).

Alpha-melanocyte-stimulating hormone (alpha-MSH), a 13 amino-acid peptide, is synthesized by keratinocytes, melanocytes, monocytes and astrocytes (Wikberg et al., 2000). This peptide derives from the pro-opiomelanocortin (POMC) after a processing by a proteolytic cascade (Pritchard & White, 2007), producing also five other peptides. Alpha-MSH acts as an AMP by inhibiting *S. aureus* and *C. albicans* growth at picomolar concentration (Cutuli et al., 2000). Interestingly, the tripeptide KPV (alpha-MSH 11-13) exhibited similar antimicrobial properties (Hiltz & Lipton, 1990; Mandrika et al., 2001; Mugridge et al., 1991), without effect on melanocytes (Sawyer et al. 1990). Alpha-MSH acts in two ways; it has a direct antimicrobial effect at very low concentration and reduces inflammatory responses associated with UV induced epithelial injury (Radek & Gallo, 2007).
