Vos J G, van Logten M J, Kreeftenberg J G, Kruizinga W
Ann N Y Acad Sci. 1979 May 31;320:535-50.
Rats were fed diets containing 0, 500, 1000, and 2000 mg HCB/kg during a 3-week period. Marked weight increases of spleen, popliteal and mesenteric lymph nodes and of the liver were found. Histologically, the white pulp in the spleen was enlarged because of an increase in size of marginal zones and follicles. In addition, there was an increase of extramedullary hemopoiesis. In the lymph nodes, the number of high endothelial venules was increased at all dose levels. The number of neutrophils, basophils and monocytes in the peripheral blood was significantly increased, whereas peripheral lymphocyte counts were slightly higher. Total serum IgM levels were markedly increased, but IgG concentrations were unaltered. On the basis of this experiment, the 1000 mg HCB/kg diet level was chosen for the different function studies that were carried out after a 3-weeks dietary regimen. Regarding the humoral immunity, IgM antibodies to LPS were unaltered, whereas primary and secondary IgM and IgG antibody titers to tetanus toxoid were increased approximately three-fold. HCB did not significantly alter the cell-mediated immunity, as shown by the following parameters: resistance to Listeria monocytogenes infection, rejection of skin transplants, and delayed-type hypersensitivity to tuberculin. The phagocytizing capacity of macrophages was studied by measuring the blood clearance of carbon particles. HCB did slightly depress the phagocytic index, but the difference with control animals was statistically not significant. The in vitro responsiveness of thymus cells to the mitogens PHA, Con A, and PWM was not changed by in vivo HCB-treatment. On a cell-for-cell basis, the responsiveness of spleen cells was increased when cultured in the presence of LPS. On a whole organ basis, the response to PHA, Con A, PWM, and LPS was markedly enhanced because of an increase in the number of nucleated spleen cells. Regarding peripheral lymphocytes, only the response to the mitogen Con A was higher. On the basis of these studies it is concluded that HCB stimulates the humoral immune response in the rat, enhances the in vitro responsiveness of spleen cells to the different mitogens mainly as a result of an increase in the number of splenic lymphocytes, but does not alter the cell-mediated immunity as shown with in vivo tests. This result contrasts with data in the literature that show that HCB suppresses the humoral and cell-mediated immunity in mice. Finally, HCB pretreatment only marginally increased the susceptibility of rats to endotoxin, whereas mice have been shown to be 20-fold more susceptible to the lethal effects of bacterial endotoxin.
在为期3周的时间里，给大鼠喂食含有0、500、1000和2000毫克六氯苯/千克的日粮。结果发现，脾脏、腘淋巴结和肠系膜淋巴结以及肝脏明显增重。组织学检查显示，脾脏白髓因边缘区和滤泡体积增大而增大。此外，髓外造血增加。在淋巴结中，所有剂量水平下高内皮微静脉的数量均增加。外周血中嗜中性粒细胞、嗜碱性粒细胞和单核细胞的数量显著增加，而外周淋巴细胞计数略有升高。血清总IgM水平显著升高，但IgG浓度未改变。基于该实验，在3周的饮食方案后，选择1000毫克六氯苯/千克的日粮水平进行不同的功能研究。关于体液免疫，对脂多糖的IgM抗体未改变，而对破伤风类毒素的初次和二次IgM及IgG抗体滴度增加了约三倍。六氯苯并未显著改变细胞介导的免疫，如下列参数所示：对单核细胞增生李斯特菌感染的抵抗力、皮肤移植排斥反应以及对结核菌素的迟发型超敏反应。通过测量碳颗粒的血液清除率来研究巨噬细胞的吞噬能力。六氯苯确实略微降低了吞噬指数，但与对照动物的差异在统计学上不显著。体内六氯苯处理并未改变胸腺细胞对丝裂原PHA、Con A和PWM的体外反应性。在细胞水平上，当在脂多糖存在下培养时，脾细胞的反应性增加。在整个器官水平上，由于有核脾细胞数量增加，对PHA、Con A、PWM和脂多糖的反应显著增强。关于外周淋巴细胞，只有对丝裂原Con A的反应更高。基于这些研究得出结论，六氯苯刺激大鼠的体液免疫反应，主要由于脾淋巴细胞数量增加而增强脾细胞对不同丝裂原的体外反应性，但如体内试验所示，并未改变细胞介导的免疫。该结果与文献数据形成对比，文献数据表明六氯苯抑制小鼠的体液免疫和细胞介导的免疫。最后，六氯苯预处理仅略微增加了大鼠对内毒素的易感性，而小鼠已被证明对细菌内毒素的致死作用的易感性高20倍。
