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 between cytotoxic and/or immunomodulative properties of 5 reference compounds: cadmium chloride (CdCl2): didodecyl-dimethyl ammonium bromide (DDAB); cyclosporin (CsA); dexamethasone (DEXA); and theophylline. Two colorimetric cytotoxicity assays were employed, the thiazolyl blue tetrazolium bromide and neutral red, and the H-thymidine DNA incorporation assay on phytohemagglutinin stimulated or non-stimulated PBL was used, as a parameter of cell mediated immunity. This study demonstrated the importance of performing colorimetric or other cytotoxicity assays before any investigation of mechanisms of action of different substances on immunomodulation and relative human risk 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 extent theophylline have immunomodulative rather than cytotoxic effects on PBL within the range of the concentrations studied.
Maravelias
C
C
Department of Forensic Medicine and Toxicology, School of Medicine, University of Athens, Greece.
Dona
A
A
Athanaselis
S
S
Koutselinis
A
A
D018931:Antineoplastic Agents, Hormonal / Q000633:toxicity; D019256:Cadmium Chloride / Q000633:toxicity; D003124:Colorimetry / Q000379:methods; D016572:Cyclosporine / Q000633:toxicity; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods*; D003907:Dexamethasone / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007166:Immunosuppressive Agents / Q000633:toxicity; D008214:Lymphocytes / Q000187:drug effects*; D000644:Quaternary Ammonium Compounds / Q000633:toxicity; D013806:Theophylline / Q000633:toxicity; D014665:Vasodilator Agents / Q000633:toxicity
D018931:Antineoplastic Agents, Hormonal; D007166:Immunosuppressive Agents; D000644:Quaternary Ammonium Compounds; D014665:Vasodilator Agents; C046112:didodecyldimethylammonium; D003907:Dexamethasone; D016572:Cyclosporine; D013806:Theophylline; D019256:Cadmium Chloride