A pivotal component of epidermal barrier formation is the synthesis within nucleated keratinocytes of the intercellular lipid bilayer, a functional permeability barrier composed of specific lipids present in proper ratio. Epidermal barrier lipids are autonomous from lipids circulating in the bloodstream and are composed predominantly of equimolar concentrations of free fatty acids, cholesterol, and ceramides (1-3,5,10-12). Within lamellar bodies (Odland bodies) located within keratinocytes of the upper epidermis, precursor epidermal lipids are used to create newly synthesized lipids which are organized into a lipid bilayer referred to as the lamellar unit membrane structure (1,10-17). Ultimately, as cornification occurs in the upper epidermis, a phospholipid-enriched plasma membrane is converted to a ceramide-rich bilayered membrane by weight (1,8,17).
The intercellular lipid bilayer matrix (“the mortar”) functions to control intercellular water movement, maintain intracellular water content, and limit TEWL. The major homeostatic signal stimulating epidermal lipid synthesis is an adverse change in epidermal barrier status, sensed as an increase in TEWL. In the presence of exogenous (i. e., use of a harsh soap) or endogenous (i. e., underlying dermatologic disease) insults that cause a loss in barrier lipids which comprise the intercellular matrix, an increased TEWL of as little as 1% produces a physiologic signal that upregulates lipid synthesis (1-3,5). Depending upon the degree of barrier insult and several other factors, normalization of barrier function may occur over a period of hours to days (1,15,17).