Direct suppression of cultured spleen cell responses by chlordane and the basis for differential effects on in vivo and in vitro immunocompetence.
Immunosuppression by gamma-chlordane was examined by the direct addition of chlordane to cultured spleen cells from untreated B6C3F1 mice. Both cell-mediated and humoral immune responses were markedly suppressed upon in vitro exposure. The mixed lymphocyte response and the proliferative response to both B- and T-cell mitogens were significantly suppressed at micromolar concentrations of chlordane. The antibody response to sheep erythrocytes (SRBC) was suppressed 90% at 10 microM chlordane. The kinetics of the SRBC response were not altered by chlordane. Addition of chlordane to the antibody cultures on various days indicated an effect at the early stages of the response. Previous studies with chlordane failed to demonstrate immunosuppression following in vivo exposure. The possibility that chlordane was metabolized in vivo to a less immunosuppressive form was studied by examining the effect of the major metabolite, oxychlordane, on the in vitro antibody response and by incubating splenocytes with chlordane and a liver S9 preparation prior to culture with SRBC. Oxychlordane was immunosuppressive by itself, and the activity of chlordane was unaltered in the co-culture experiments. The association of chlordane with serum components was evaluated in vitro in cultures of mouse bone-marrow cells (BMC). The chlordane-induced suppression of [3H]thymidine incorporation by BMC was reversed by the addition of mouse or human serum. In summary, chlordane produces marked suppression of in vitro immune responses via an apparent antiproliferative action. The failure of chlordane to produce in vivo immunosuppression may be related to extensive association of chlordane with serum components.
Department of Pharmacology and Toxicology, Medical College of Virginia/Virginia Commonwealth University, Richmond.
K W
KW
Johnson
N E
NE
Kaminski
A E
AE
Munson
D000818:Animals; D001711:Biotransformation; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002478:Cells, Cultured; D002706:Chlordan / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity*; D004261:DNA Replication / Q000187:drug effects; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D007121:Immunocompetence / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology
D002706:Chlordan; C008743:oxychlordane