Relevance of in vitro tests to in vivo acute skin inflammation: potential in vitro applications of skin keratome slices, neutrophils, fibroblasts, mast cells and macrophages.
In vitro tests on cells or keratome slices of skin may reproduce, or indirectly reflect, the first event in acute inflammation, the cytotoxic action of an irritant on epithelial/epidermal cells. Keratome slices of human or animal skin release enzymes, show histochemical changes and demonstrate increased or decreased utilization of isotope-labelled amino acids when exposed to chemicals, including surfactants, or bacterial toxins (Clostridium perfringens). The correlation with in vivo change is good for weak irritants and moderate to poor for strong irritants. Corrosive substances destroy the ability of the tissue to respond. Similar results have been obtained in tests on fibroblast cultures without or with an agar-keratin barrier. Neutrophils, or their separated granules, and mast cells have limited application in the prediction of chemical irritancy. The relevance and limitations of in vitro toxicological predictive tests are assessed in terms of the in vivo feature reflected by the in vitro test, the range of chemicals active in vitro compared to the in vivo responses, the ability to discriminate between intensities of reactions and the need for standards to compare results in different laboratories.