Rodgers K E, Haviland D L, Ware C F
Division of Biomedical Sciences, University of California, Riverside 92521-0121.
Immunopharmacology. 1989 May-Jun;17(3):131-40. doi: 10.1016/0162-3109(89)90041-6.
Acute administration of nontoxic doses of an impurity in technical malathion, O,O,S-trimethyl phosphorothioate (OOS-TMP), was able to block the in vitro generation of cytotoxic T lymphocytes (CTL) to alloantigen and antibody-secreting cells (Ab) to sheep red blood cells (SRBC). The effects of an antagonist of the delayed toxicity and lung damage of OOS-TMP, O,O,O-trimethyl phosphorothionate (OOO-TMP), and pretreatment of tolerance-inducing doses of OOS-TMP on OOS-TMP-induced immune suppression were examined. Treatment groups included (A) acute administration of OOO-TMP, (B) coadministration of OOO-TMP with OOS-TMP (at concentrations which have been shown previously to block lung toxicity). (C) repeated (4 x on consecutive days) administration of OOS-TMP (which was shown previously to block a lung toxicity which occurs following a challenge with OOS-TMP) and (D) repeated administration of OOS-TMP followed by a challenge dose of OOS-TMP 24 h before death. There was no change in lymphoid organ size following any of these treatments. However, splenocytes from animals that were exposed to treatment regimes A, B and D had significantly elevated proliferative responses to mitogens concanavalin A (ConA) and lipopolysaccharide (LPS). The ability of splenocytes to generate an Ab response to SRBC was significantly elevated following treatment regime A and at the lower dose in treatment regime D. All other treatment protocols did not alter this immune parameter. There was no difference in the ability of splenocytes to generate a CTL response following these treatment regimes. In conclusion, the degree of protection from immune suppression by these treatments which have been shown to protect against lung toxicity varied with the sensitivity of the immune parameters to suppression by acute administration of OOS-TMP.
急性给予技术马拉硫磷中的一种无毒剂量杂质O,O,S-三甲基硫代磷酸酯（OOS-TMP），能够阻断体外针对同种异体抗原产生细胞毒性T淋巴细胞（CTL）以及针对绵羊红细胞（SRBC）产生抗体分泌细胞（Ab）。研究了OOS-TMP延迟毒性和肺损伤的拮抗剂O,O,O-三甲基硫代磷酸酯（OOO-TMP）的作用，以及给予诱导耐受性剂量的OOS-TMP预处理对OOS-TMP诱导的免疫抑制的影响。治疗组包括：（A）急性给予OOO-TMP；（B）将OOO-TMP与OOS-TMP共同给药（浓度为先前已证明可阻断肺毒性的浓度）；（C）重复（连续4天，每天1次）给予OOS-TMP（先前已证明可阻断OOS-TMP激发后出现的肺毒性）；（D）重复给予OOS-TMP，然后在处死前24小时给予一次激发剂量的OOS-TMP。这些处理后，淋巴器官大小均无变化。然而，接受处理方案A、B和D的动物的脾细胞对有丝分裂原刀豆球蛋白A（ConA）和脂多糖（LPS）的增殖反应显著升高。处理方案A以及处理方案D中较低剂量处理后，脾细胞对SRBC产生Ab反应的能力显著提高。所有其他处理方案均未改变这一免疫参数。这些处理方案后，脾细胞产生CTL反应的能力没有差异。总之，这些已证明可预防肺毒性的处理对免疫抑制的保护程度，随免疫参数对急性给予OOS-TMP抑制的敏感性而变化。
