Johnson K W, Kaminski N E, Munson A E
Department of Pharmacology and Toxicology, Medical College of Virginia/Virginia Commonwealth University, Richmond.
J Toxicol Environ Health. 1987;22(4):497-515. doi: 10.1080/15287398709531089.
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.
通过将氯丹直接添加到未处理的B6C3F1小鼠的培养脾细胞中来检测γ-氯丹的免疫抑制作用。体外暴露后，细胞介导的免疫反应和体液免疫反应均受到明显抑制。在微摩尔浓度的氯丹作用下，混合淋巴细胞反应以及对B细胞和T细胞有丝分裂原的增殖反应均受到显著抑制。在10微摩尔氯丹作用下，对绵羊红细胞（SRBC）的抗体反应被抑制了90%。氯丹并未改变SRBC反应的动力学。在不同天数向抗体培养物中添加氯丹表明其在反应早期具有作用。先前关于氯丹的研究未能证明体内暴露后存在免疫抑制作用。通过检测主要代谢产物氧化氯丹对体外抗体反应的影响，以及在用SRBC培养之前将脾细胞与氯丹和肝脏S9制剂共同孵育，研究了氯丹在体内代谢为免疫抑制性较低形式的可能性。氧化氯丹本身具有免疫抑制作用，并且在共培养实验中氯丹的活性未改变。在小鼠骨髓细胞（BMC）培养物中体外评估了氯丹与血清成分的结合情况。添加小鼠或人血清可逆转氯丹诱导的BMC对[3H]胸腺嘧啶核苷掺入的抑制作用。总之，氯丹通过明显的抗增殖作用对体外免疫反应产生显著抑制。氯丹未能产生体内免疫抑制作用可能与氯丹与血清成分的广泛结合有关。
