Xu W, Flick T, Mitchell J, Knowles C, Ault K
Maine Medical Center Research Institute, South Portland 04106, USA.
Int J Immunopharmacol. 1998 Dec;20(12):737-49. doi: 10.1016/s0192-0561(98)00061-7.
This study used a mouse model including both sexes to assess the impact of repeat cocaine exposure on the differentiation and function of T cell in thymus. Cocaine hydrochloride in 0.9% saline, 5 mg or 40 mg/kg, was administrated by i.p. injection to C57BL/6 mice for 10 days. Thymocytes were obtained 24 h after the 10th injection. Repeat in vivo cocaine exposure inhibited the proliferation of T lymphocytes in response to Con-A and Con-A plus anti-CD28. The proliferation induced by IL-2 in the Con-A stimulated T blasts was attenuated in cocaine treated mice. These effects were seen at a lower cocaine dose in female mice. The total number of thymocytes was reduced. Although the percentage of mature thymocytes (CD4+ CD8- and CD4- CD8+ cells) was not altered, the absolute cell numbers were attenuated. Both percentage and absolute cell number of immature thymocytes (CD4+ CD8+) decreased and the pre-mature (CD4- CD8-) cells increased. CD28 and CD25 expression were attenuated in Con-A stimulated thymocytes of mice treated with cocaine at 40 mg/kg. Interleukin 2 production was not significantly altered, however, gamma-IFN production was decreased by cocaine exposure at 40 mg/kg. In conclusion, cocaine exerts inhibitory effects on the function of mature thymocytes, and on the differentiation of thymocytes. A gender difference in response to cocaine was noted in that female mice were more sensitive to lower dose of cocaine exposure.
本研究使用了包含雌雄两性的小鼠模型,以评估反复接触可卡因对胸腺中T细胞分化和功能的影响。将0.9%盐水中的盐酸可卡因,以5毫克或40毫克/千克的剂量腹腔注射给C57BL/6小鼠,持续10天。在第10次注射后24小时获取胸腺细胞。体内反复接触可卡因抑制了T淋巴细胞对刀豆蛋白A(Con-A)以及Con-A加抗CD28的增殖反应。在可卡因处理的小鼠中,Con-A刺激的T母细胞中由白细胞介素-2(IL-2)诱导的增殖减弱。在雌性小鼠中,较低剂量的可卡因就能观察到这些效应。胸腺细胞总数减少。虽然成熟胸腺细胞(CD4+CD8-和CD4-CD8+细胞)的百分比没有改变,但绝对细胞数量减少。未成熟胸腺细胞(CD4+CD8+)的百分比和绝对细胞数量均下降,而早熟(CD4-CD8-)细胞增加。在接受40毫克/千克可卡因处理的小鼠的Con-A刺激的胸腺细胞中,CD28和CD25的表达减弱。白细胞介素-2的产生没有显著改变,然而,40毫克/千克的可卡因暴露使γ-干扰素的产生减少。总之,可卡因对成熟胸腺细胞的功能以及胸腺细胞的分化具有抑制作用。观察到对可卡因反应存在性别差异,即雌性小鼠对较低剂量的可卡因暴露更敏感。