ABSTRACT:Epidermal innate immunity is a complex process involving a balance of pro-and anti-inflammatory cytokines, structural proteins, and specific antigen presenting cells occurring against a background of neuroendocrine modulators such as cortisol. In this study, a multiplex array system was used to simultaneously determine multiple molecular factors critical for development of epidermal innate immune function from the skin surface of premature and term infants, healthy adults, and vernix caseosa. Samples were analyzed for Keratin 1,10,11, Keratin 6, involucrin, albumin, fibronectin and cortisol, and cytokines IL-1, TNF␣, IL-6, IL-8, MCP1, IP10, IFN␥, and IL-1 receptor antagonist. Keratin 1,10,11 was decreased and involucrin was increased in infants versus adults. All infants had elevated IL1␣ and reduced TNF␣ versus adults. IL-6, IL-8, and MCP1 were significantly increased in premature versus term infants and adults. Skin surface cortisol and albumin were significantly elevated in premature infants. The biomarker profile in premature infants was unique with differences in structural proteins, albumin, and cytokines IL-6, IL-1␤, IL-8, and MCP1. The higher infant IL1␣ may be associated with skin barrier maturation. The significant elevations in skin surface cortisol for preterm infants may reflect a neuroendocrine response to the stress of premature birth. (Pediatr Res 67: 382-386, 2010)