In vitro exposure effects of cyclosporin A and bis(tri-n-butyltin)oxide onlymphocyte proliferation, cytokine (receptor) mRNA expression, and cell surface marker expression in rat thymocytes and splenocytes

Rat thymocytes and splenocytes were exposed in vitro to the model compounds Cyclosporin A (CsA), an immunosuppressive drug, and bis(tri-n-butyltin)oxi de (TBTO), an immunotoxic environmental contaminant. The lymphocyte transfo rmation test (LTT), cytokine (receptor) mRNA expression (RT-PCR and dot blo t hybridisation), and flow cytometry were evaluated as assays for in vitro immunotoxicity,at dose levels that did not show effects on viability, this being the aim of the study. LTT and RT-PCR proved useful assays. Lymphocyte transformation was suppressed by both compounds, while IL-2 mRNA expressio n was suppressed by CsA but not by TBTO, and both compounds suppressed IL-2 R mRNA expression in splenocytes but not in thymocytes. Furthermore, the da ta obtained suggest that antiproliferative effects may be more relevant tha n apoptosis induction for TBTO induced thymus atrophy. (C) 1999 Elsevier Sc ience Ireland Ltd. All rights reserved.