Expression of cutaneous immunity markers during infant skin maturation.

BACKGROUND/OBJECTIVES: Infant skin undergoes a maturation process during the early years of life. Little is known about the skin's innate immunity. We investigated the dynamics of innate immunity markers collected from the surface of infant skin during the first 36 months of life. METHODS: A total of 117 healthy infants aged 3-36 months participated in the study. We extracted human beta defensin-1 and interleukin 1 alpha and its receptor antagonist using transdermal analysis patches from the skin surface of the posterior lower leg area. The extracts were analyzed using a spot enzyme-linked immunosorbent assay. RESULTS: Skin surface human beta defensin-1 levels were higher early in life and decreased with infant age. The ratio of interleukin 1 alpha receptor antagonist to interleukin 1 alpha did not change significantly with age but showed a distinct difference between sexes, with female infants having higher values than male infants. CONCLUSION: As is the case with skin structure and functional properties, cutaneous innate immunity also appears to undergo a maturation period during infancy, with innate immunity slowly declining as adaptive immunity takes over. Sex differences in immune markers may explain sex-dependent susceptibilities to infection.

Further development of an in vitro model for studying the penetration of chemicals through compromised skin.

A new in vitro model based on the electrical resistance properties of the skin barrier has been established in this laboratory. The model utilises a tape stripping procedure in dermatomed pig skin that removes a specific proportion of the stratum corneum, mimicking impaired barrier function observed in humans with damaged skin. The skin penetration and distribution of chemicals with differing physicochemical properties, namely; Benzoic acid, 3-Aminophenol, Caffeine and Sucrose has been assessed in this model. Although, skin penetration over 24h differed for each chemical, compromising the skin did not alter the shape of the time course profile, although absorption into receptor fluid was higher for each chemical. Systemic exposure (receptor fluid, epidermis and dermis), was marginally higher in compromised skin following exposure to the fast penetrant, Benzoic acid, and the slow penetrant Sucrose. The systemically available dose of 3-Aminophenol increased to a greater extent and the absorption of Caffeine was more than double in compromised skin, suggesting that Molecular Weight and Log Pow, are not the only determinants for assessing systemic exposure under these conditions. Although further investigations are required, this in vitro model may be useful for prediction of dermal route exposure under conditions where skin barrier is impaired.

Hard water softening effect of a baby cleanser.

BACKGROUND: Hard water is associated with atopic dermatitis (eczema). We wanted to determine if a baby cleanser and its individual components altered free ionized calcium (Ca2+) in a simulated hard water baby bath. For these studies, an in vitro determination of free Ca2+ in a simulated hard water baby bath, and an in vivo exploratory study of free Ca2+ absorption into skin from hard water were performed. METHODS: Free Ca2+ was measured with an ion-sensitive electrode in vitro in hard water (100-500 ppm, Ca2+) before and after addition of the cleanser and/or its components. In an exploratory study, absorption of Ca2+ into skin from hard water was determined in three female participants (aged 21-29 years). RESULTS: At an in-use dilution of 1%, the test cleanser reduced free Ca2+ from ~500 ppm to <200 ppm; a 10% in-use dilution bound virtually all free Ca2+. The anionic surfactant component contributed the most to this effect. In the exploratory in vivo study, we measured a reduction of ~15% in free Ca2+ from simulated hard water over 10 minutes. CONCLUSION: Baby cleansers can bind free Ca2+ and reduce the effective water hardness of bath water. Reducing the amount of free Ca2+ in the water will reduce the availability of the ion for binding to the skin. Altering or reducing free Ca2+ concentrations in bath water may be an important parameter in creating the ideal baby bath.

Developmental Changes in Skin Barrier and Structure during the First 5 Years of Life.

The structure of the stratum corneum (SC) and the corresponding skin barrier develops from before birth up to about 4 years of age. Large subject-to-subject variability within an age group requires a large population to observe trends in skin barrier properties over time. Barrier function, quantified by transepidermal water loss (TEWL) and SC thickness, was measured on the upper inner arm and dorsal forearm in subjects aged 3 months to 4 years (n = 171) and a subset of mothers (n = 44). The rate of skin surface area expansion as a function of age peaked before birth (∼90 cm2/week) and declined to a steady plateau (∼10 cm2/week) by 1 year of age. SC thickness increased and TEWL decreased, but did not reach adult values until 3-4 years of age. A better understanding of how skin hydration changes after birth suggests that barrier function may be related mechanistically to skin surface area expansion.

In vitro assessment of skin irritation potential of surfactant-based formulations by using a 3-D skin reconstructed tissue model and cytokine response.

The personal care industry is focused on developing safe, more efficacious, and increasingly milder products, that are routinely undergoing preclinical and clinical testing before becoming available for consumer use on skin. In vitro systems based on skin reconstructed equivalents are now established for the preclinical assessment of product irritation potential and as alternative testing methods to the classic Draize rabbit skin irritation test. We have used the 3-D EpiDerm™ model system to evaluate tissue viability and primary cytokine interleukin-1α release as a way to evaluate the potential dermal irritation of 224 non-ionic, amphoteric and/or anionic surfactant-containing formulations, or individual raw materials. As part of our testing programme, two representative benchmark materials with known clinical skin irritation potential were qualified through repeated testing, for use as references for the skin irritation evaluation of formulations containing new surfactant ingredients. We have established a correlation between the in vitro screening approach and clinical testing, and are continually expanding our database to enhance this correlation. This testing programme integrates the efforts of global manufacturers of personal care products that focus on the development of increasingly milder formulations to be applied to the skin, without the use of animal testing.

Geometrical and topological analysis of in vivo confocal microscopy images reveals dynamic maturation of epidermal structures during the first years of life.

Reflectance confocal microscopy is successfully used in infant skin research. Infant skin structure, function, and composition are undergoing a maturation process. We aimed to uncover how the epidermal architecture and cellular topology change with time. Images were collected from three age groups of healthy infants between one and four years of age and adults. Cell centers were manually identified on the images at the stratum granulosum (SG) and stratum spinosum (SS) levels. Voronoi diagrams were used to calculate geometrical and topological parameters. Infant cell density is higher than that of adults and decreases with age. Projected cell area, cell perimeter, and average distance to the nearest neighbors increase with age but do so distinctly between the two layers. Structural entropy is different between the two strata, but remains constant with time. For all ages and layers, the distribution of the number of nearest neighbors is typical of a cooperator network architecture. The topological analysis provides evidence of the maturation process in infant skin. The differences between infant and adult are more pronounced in the SG than SS, while cell cooperation is evident in all cases of healthy skin examined.

Topically applied ceramide accumulates in skin glyphs.

Ceramides (CERs), structural components of the stratum corneum (SC), impart essential barrier properties to this thin outer layer of the epidermis. Variations in CER species within this layer have been linked to several skin diseases. A recent proliferation of CER-containing topical skin-care products warrants the elucidation of CER penetration profiles in both healthy and diseased skin. In the current study, the spatial distributions of CER concentration profiles, following topical application of two species of CER, were tracked using infrared imaging. Suspensions of single-chain perdeuterated sphingosine and phytosphingosine CER in oleic acid were applied, in separate experiments, to the surface of healthy intact ex vivo human skin using Franz diffusion cells. Following either a 24- or 48-hour incubation period at 34°C, infrared images were acquired from microtomed skin sections. Both CER species accumulated in glyph regions of the skin and penetrated into the SC, to a limited extent, only in these regions. The concentration profiles observed herein were independent of the CER species and incubation time utilized in the study. As a result, a very heterogeneous, sparse, spatial distribution of CERs in the SC was revealed. In contrast, oleic acid was found to be fairly homogeneously distributed throughout the SC and viable epidermis, albeit at lower concentrations in the latter. A more uniform, lateral distribution of CERs in the SC would likely be important for barrier efficacy or enhancement.

New insights about infant and toddler skin: implications for sun protection.

The skin is increasingly recognized as a component of the innate immune response, in addition to its role as a physical barrier. Although the deleterious effects of solar ultraviolet radiation (UVR), including immunosuppression and cutaneous tumorigenesis, are widely acknowledged, most studies to date have concentrated on adult skin. Despite the more sensitive nature of infant and toddler skin, little is known about its responses to UVR exposure, whether acute or long-term. Accumulating evidence suggests not only that the skin's barrier protection remains immature throughout at least the first 2 years of life but also that accumulation of UVR-induced changes in the skin may begin as early as the first summer of life. Such evidence not only affirms the importance of sun protection during the infant and toddler years but underscores the need for more research to establish evidence-based standards of care in this area. In this article we review recent studies in which differences between the skin properties of infants and young children and those of adults were compared, and we discuss the implications of these differences for sun-protection practices.