Navarro H A, Basta P V, Seidler F J, Slotkin T A
Center for Chemistry and Life Sciences, Research Triangle Institute, Research Triangle Park, NC 27709, USA.
Brain Res Dev Brain Res. 2001 Oct 24;130(2):249-52. doi: 10.1016/s0165-3806(01)00254-1.
Neural input plays a key role in the establishment of immune function, and environmental agents or drugs that interfere with the development of the nervous system elicit corresponding immunologic deficits. In the current study, we gave neonatal rats the widely used organophosphate pesticide, chlorpyrifos (CPF), and determined the immediate and long-term effects on T-lymphocyte function. Exposure of neonatal rats to 1 mg/kg of CPF daily on postnatal days (PN) 1-4 had no immediate effect (PN5) on T-cell mitogenic responses to concanavalin A challenge. However, once the animals reached adulthood, T-cell responses were significantly impaired. There were no deficits in basal T-cell replication rates, implying that the adverse effect of CPF exposure was specific to mitogenic activation. Treatment during a later neonatal period (PN11-14) elicited similar deficits in adulthood. CPF administration leads to inhibition of cholinesterase, and a cholinergic connection is supported by the fact that the results seen here correspond to those seen with a direct cholinergic stimulant (nicotine) administered during gestation or adolescence. These results indicate that exposure to CPF during a developmental period in which this organophosphate pesticide is known to produce lasting changes in neural function, elicits corresponding, long-term deficits in immune competence.
神经输入在免疫功能的建立中起着关键作用，而干扰神经系统发育的环境因素或药物会引发相应的免疫缺陷。在本研究中，我们给新生大鼠使用了广泛使用的有机磷农药毒死蜱（CPF），并确定了其对T淋巴细胞功能的即时和长期影响。新生大鼠在出生后第1至4天每天暴露于1mg/kg的CPF，对刀豆球蛋白A刺激的T细胞有丝分裂反应在出生后第5天没有即时影响。然而，一旦动物成年，T细胞反应就会显著受损。基础T细胞复制率没有缺陷，这意味着CPF暴露的不良影响是特定于有丝分裂激活的。在新生儿后期（出生后第11至14天）进行治疗，成年后也会出现类似的缺陷。CPF的施用会导致胆碱酯酶的抑制，胆碱能联系得到了以下事实的支持：此处观察到的结果与在妊娠或青春期施用直接胆碱能兴奋剂（尼古丁）时观察到的结果一致。这些结果表明，在已知这种有机磷农药会对神经功能产生持久变化的发育时期暴露于CPF，会引发相应的长期免疫能力缺陷。
