The search for novel anti-inflammatory compounds that can be successfully formulated into either prescription or cosmetic topical products that show efficacy in treating dermatological conditions requires the availability of appropriate skin cell culture-based assays. Clearly, the cell types needed for such studies must include, at a minimum, normal human keratinocyte and fibroblast cell strains. In addition, because chronic skin inflammatory disease involves the activity of immune cells, cultures of human monocytes and T-lymphocytes should also be incorporated into the screening strategy. Finally, when one considers the important role that adhesion molecules, expressed on the surface of endothelial cells, play in directing leukocytes into the skin, being able to assess the effect of putative anti-inflammatory compounds on adhesion molecule expression in cultured endothelial cells would add an additional important screening capability.
Once the cell culture models have been established, the appropriate screening assays must be selected. These screens should focus on the effect that a potential antiinflammatory molecule has on the expression of one or more key inflammatory mediators. Due to the fact that one of the most common activators of skin inflammation is sunlight, specifically UVB radiation, the determination of a compound’s ability to block the induction of pro-inflammatory PGE-2 by UVR in both keratinocytes and fibroblasts represents a logical first step in the screening process. In addition, because skin inflammation is often triggered by contact with chemical irritants or allergens, the use of tetradecanoylphorbol acetate (TPA), which is a potent “irritant” stimulator of inflammatory mediators in skin, provides an additional model for the analysis of anti-inflammatory activities of test compounds. Finally, because IL-1 is one of the most important mediators and propagators of inflammation and is rapidly induced by an inflammatory stimulus, such as UVR, determining the ability of a potential anti-inflammatory compound to block either the production or action of IL-1 is a critically important initial screening study (68-70).