An increased (less acidic) pH can activate proteases with neutral-to-alkaline pH optima to process inactive forms of IL-1α, IL-1β, and IL-18 that are stored in the cytosol of corneocytes.16,38-41 Consistent with this view, Hosomi et al42 showed increased activity of caspase-1 in the SC of patients with Netherton syndrome, an autosomal recessive inherited disease characterized by features of AD and uninhibited breakdown of filaggrin in the SC. This evidence concerns the gene IL18 and Netherton syndrome.