The importance of performing in vitro cytotoxicity testing before immunomodulation evaluation

This study uses the well known sensitive and reproducible human peripheral blood lymphocyte (PBL) assay as a model for the possible discrimination bet ween cytotoxic and/or immunomodulative properties of 5 reference compounds: cadmium chloride (CdCl2): didodecyl-dimethyl ammonium bromide (DDAB):cyclo sporin (CsA); dexamethasone (DEXA): and theophylline. Two colorimetric cyto toxicity assays were employed, the thiazolyl blue tetrazolium bromide and n eutral red, and the H-3-thymidine DNA incorporation assay on phytohemagglut inin stimulated or non-stimulated PBL was used, as a parameter of cell medi ated immunity. This study demonstrated the importance of performing colorim etric or other cytotoxicity assays before any investigation of mechanisms o f action of different substances on immunomodulation and relative human ris k assessment. This study showed that CdCl2 and DDAB have a cytotoxic rather than immunomodulative effect on PBL and that CsA. DEXA and to a lesser ext ent theophylline have immunomodulative rather than cytotoxic effects on PBL within the range of the concentrations studied.