Immunocompetent cells for in vitro screening of skin irritation

Abstract

The present studies were aimed at evaluating procedures for assessing the immunmodulatory effects of chemicals and preparations on macrophage differentiation and lymphocyte proliferation in cell cultures. The effects of 10 drugs and anti-inflammatory agents were monitored by determining thymidine incorporation into phytohaemagglutinin (PHA)-stimulated T cells in the lymphocyte transformation test (LTT) and the expression of two surface antigens on macrophages in the macrophage differentiation assay (MDA). One antigen was found on macrophages in acute inflamed tissue. The other was detected on those found in recovering tissue. These parameters were compared with mean skin irritation scores for 12 known cosmetic products from epicutaneous patch testing. Finally, these parameters were also used to study six cosmetic test formulae with unknown irritation potentials subjected to blind testing during phase 2 of the “CTFA Evaluation of Alternatives Program”. Immunosuppressive agents were detected in both systems. Agents, thought to be pro-inflammatory, were monitored in the MDA by the acute inflammation marker. Skin irritation scores of known preparations correlated well with those of expressed acute inflammation markers in the MDA ( r s = 0.714), but no clear relationship was detectable in the LTT. In contrast one of the CTFA samples tested blind revealed a strong response in both tests. The roll-on antiperspirant stimulated T-cell proliferation and induce a strong expression of the acute inflammation marker on macrophages. Based on these findings further studies are in progress to evaluate the usefulness of these in vitro tests for predicting dermal irritation.