Thuvander A, Funseth E, Breitholtz-Emanuelsson A, Hallén I P, Oskarsson A
Toxicology Division, Swedish National Food Administration, Uppsala, Sweden.
Nat Toxins. 1996;4(3):141-7. doi: 10.1002/19960403nt7.
Effects on the immune system after perinatal exposure to ochratoxin A (OA) were studied in Sprague-Dawley rats after single or repeated exposure of the dams. In a short-term study, dams with litters were given a single dose of OA (0, 10, 50 or 250 micrograms/kg body weight) on day 11 of lactation. The effects on cell numbers in spleen and thymus añd on the mitogen responses of lymphocytes were evaluated in the suckling pups on day 14 of lactation. The proliferative response of splenocytes to the T-cell mitogen Concanavalin A (Con A) was significantly stimulated in pups from dams given 10 or 50 micrograms OA/kg body weight as compared to control pups. In addition, proliferation of thymocytes in response to Con A was stimulated in pups from dams exposed to 50 micrograms OA/kg body weight. In a long-term, cross-fostering study comparing pre- and postnatal exposure, half of the dams received 50 micrograms OA/kg body weight 5 days a week by gastric intubation 2 weeks before mating, during gestation and then 7 days a week until weaning. Effects on immune parameters were studied in the pups on day 14 of lactation and at 13 weeks of age. Suppressed mitogenic responses were seen to both lipopolysaccharide (LPS) and Con A in prenatally exposed pups sampled on day 14 of lactation. At 13 weeks the response of splenocytes to LPS was still impaired. The primary antibody response to a viral antigen was also lower in the prenatally exposed pups than in the control pups. These effects on the immune response were not seen in the groups of pups exposed postnatally or both pre- and postnatally, although blood concentrations of OA were higher in these groups at the time of the first sampling. This indicates that the decrease in proliferation and antibody production resulted from prenatal modulation of the immune system. The results show that prenatal exposure to relatively low doses of OA may induce immunosuppression. In contrast, short-term exposure of suckling pups to OA via the milk stimulates the proliferative responses of lymphocytes to polyclonal activation.
在对斯普拉格-道利大鼠的母鼠进行单次或重复接触赭曲霉毒素A（OA）后，研究了围产期接触OA对其免疫系统的影响。在一项短期研究中，哺乳期第11天给带仔母鼠单次注射OA（0、10、50或250微克/千克体重）。在哺乳期第14天评估对哺乳幼崽脾脏和胸腺细胞数量以及淋巴细胞丝裂原反应的影响。与对照幼崽相比，给予10或50微克OA/千克体重的母鼠所产幼崽的脾细胞对T细胞丝裂原刀豆球蛋白A（Con A）的增殖反应受到显著刺激。此外，接触50微克OA/千克体重的母鼠所产幼崽的胸腺细胞对Con A的增殖反应也受到刺激。在一项比较产前和产后接触情况的长期交叉寄养研究中，一半的母鼠在交配前2周、妊娠期每周5天通过胃管给予50微克OA/千克体重，然后在哺乳期每周7天直至断奶。在哺乳期第14天和13周龄时研究对幼崽免疫参数的影响。在哺乳期第14天采集的产前接触幼崽中，对脂多糖（LPS）和Con A的丝裂原反应均受到抑制。在13周时，脾细胞对LPS的反应仍然受损。产前接触幼崽对病毒抗原的初次抗体反应也低于对照幼崽。在产后接触或产前和产后均接触的幼崽组中未观察到这些对免疫反应的影响，尽管在首次采样时这些组的OA血药浓度较高。这表明增殖和抗体产生的减少是由免疫系统的产前调节引起的。结果表明，产前接触相对低剂量的OA可能会诱导免疫抑制。相比之下，哺乳幼崽通过乳汁短期接触OA会刺激淋巴细胞对多克隆激活的增殖反应。
