In vitro exposure effects of cyclosporin A and bis(tri-n-butyltin)oxide on lymphocyte 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)oxide (TBTO), an immunotoxic environmental contaminant. The lymphocyte transformation test (LTT), cytokine (receptor) mRNA expression (RT-PCR and dot blot 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 expression was suppressed by CsA but not by TBTO, and both compounds suppressed IL-2R mRNA expression in splenocytes but not in thymocytes. Furthermore, the data obtained suggest that antiproliferative effects may be more relevant than apoptosis induction for TBTO induced thymus atrophy.
Vandebriel
R J
RJ
Laboratory for Pathology and Immunobiology, National Institute of Public Health and the Environment, Bilthoven, The Netherlands. r.vandebriel@rivm.nl
Spiekstra
S W
SW
Hudspith
B N
BN
Meredith
C
C
Van Loveren
H
H
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000187:drug effects*; D015704:CD4 Antigens / Q000096:biosynthesis / Q000187:drug effects; D016827:CD8 Antigens / Q000096:biosynthesis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D009693:Nucleic Acid Hybridization / Q000379:methods; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015375:Receptors, Interleukin-2 / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014220:Trialkyltin Compounds / Q000494:pharmacology
D015703:Antigens, CD; D015704:CD4 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D014220:Trialkyltin Compounds; D016753:Interleukin-10; C005961:bis(tri-n-butyltin)oxide; D007371:Interferon-gamma; D016572:Cyclosporine