Masten S A, Millard W J, Karlix J L, Shiverick K T
Department of Pharmacology and Therapeutics, University of Florida, Gainesville, USA.
J Pharmacol Exp Ther. 1996 May;277(2):1090-6.
This study examined the effect of chronic cocaine exposure on selected immune parameters in pregnant rats. Cocaine hydrochloride, 60 mg/kg, was administered by i.p. injection as a divided daily dose on gestation days 8 to 19. This cocaine treatment regimen did not result in any change in maternal body weight, spleen and thymus body weight ratios or lymphocyte recovery from these organs. Cocaine treatment had no effect on the plasma levels of prolactin, growth hormone and insulin-like growth factor-1; hormones with immunoregulatory potential. In contrast, the plasma immunoglobulin G concentration in cocaine-treated animals was 48% higher (P < .05) than in control animals. Spleen lymphocytes and thymocytes were isolated and evaluated for their proliferative responses in vitro to a panel of T and B cell mitogens. Lymphocytes from cocaine-treated animals showed no significant differences in proliferative responses to concanavalin A (conA), phytohemagglutinin, pokeweed mitogen, interleukin-2 or lipopolysaccharide. The ability of conA-stimulated spleen lymphocytes to synthesize and secrete prolactin-immunoreactive proteins was further assessed by Western immunoblotting. We found that conA-stimulated spleen lymphocytes from cocaine-treated animals showed significantly decreased levels of intracellular and secreted 44,000-mw prolactin-immunoreactive proteins. In contrast, conA-stimulated spleen lymphocytes from control and cocaine-treated groups secreted equivalent amounts of the cytokine interleukin-2. In conclusion, chronic administration of cocaine to female rats during pregnancy significantly altered serum immunoglobulin G levels and lymphocyte production of prolactin-immunoreactive proteins in the absence of changes in lymphocyte proliferation in response to mitogens.
本研究检测了孕期大鼠长期接触可卡因对特定免疫参数的影响。在妊娠第8至19天,以每天分次腹腔注射的方式给予盐酸可卡因,剂量为60mg/kg。这种可卡因治疗方案并未导致母鼠体重、脾脏和胸腺体重比或这些器官淋巴细胞恢复情况发生任何变化。可卡因治疗对催乳素、生长激素和胰岛素样生长因子-1的血浆水平没有影响;这些激素具有免疫调节潜能。相比之下,接受可卡因治疗的动物血浆免疫球蛋白G浓度比对照动物高48%(P<0.05)。分离脾脏淋巴细胞和胸腺细胞,并评估它们在体外对一组T细胞和B细胞有丝分裂原的增殖反应。来自接受可卡因治疗动物的淋巴细胞在对刀豆球蛋白A(conA)、植物血凝素、商陆有丝分裂原、白细胞介素-2或脂多糖的增殖反应上没有显著差异。通过蛋白质免疫印迹法进一步评估了conA刺激的脾脏淋巴细胞合成和分泌催乳素免疫反应性蛋白的能力。我们发现,来自接受可卡因治疗动物的conA刺激的脾脏淋巴细胞中,细胞内和分泌的44000道尔顿催乳素免疫反应性蛋白水平显著降低。相比之下,来自对照组和接受可卡因治疗组的conA刺激的脾脏淋巴细胞分泌等量的细胞因子白细胞介素-2。总之,孕期对雌性大鼠长期给予可卡因,在不改变淋巴细胞对有丝分裂原增殖反应的情况下,显著改变了血清免疫球蛋白G水平以及淋巴细胞催乳素免疫反应性蛋白的产生。