Botros S S, Makary E A, Ahmed K M, Ibrahim A M, Nashed N N, El-Nahal H M, Doughty B L, Hassanein H I
Pharmacology, Parasitology and Immunology Departments, Theodor Bilharz Institute, P.O. Box 30, Imbaba, 12411, Guiza, Egypt.
Int J Immunopharmacol. 2000 Nov;22(11):979-88. doi: 10.1016/s0192-0561(00)00062-x.
This study was undertaken to evaluate the effect of recombinant Schistosoma mansoni-26 Glutathione S-transferase (rSm 26 GST) or soluble egg antigen (SEA) alone and in addition to praziquantel (PZQ) on the state of resistance to S. mansoni reinfection. The associated changes in the immune responses were evaluated. The experimental group of mice were injected intravenously before S. mansoni infection (80 cercariae/mouse) either with rSm26 GST (1 microgx4) or SEA (10 microgx4) in addition to PZQ (2x500 mg/kg) administered 6 weeks post-infection. Seven control groups were used, three of them were the infected (80 cercariae/mouse), the challenged (240 cercariae/mouse) and the infected challenged controls (80+240 cercariae/mouse). The rest of the four groups were the treated controls receiving: the GST-Lyzate, rSmGST, SEA and PZQ in the same doses and at the same timings. Challenge infection was conducted for all the groups 8 weeks post-infection. Animals were sacrificed 3 weeks post-challenge. After sacrifice animals were perfused and percentage resistance to reinfection was calculated. Immune responses were assessed by the measurement of hepatic granuloma diameter, intralesional T-cell phenotypes and serum immunoglobulin isotypes. The highest percentage of resistance to reinfection was observed in rGST-treated group while the lowest percentage of resistance was detected in PZQ-treated group. Whereas in mice receiving combined rGST or SEA and PZQ, percentage resistance to reinfection was significantly higher than that in PZQ treated mice. The remarkable reduction in granuloma diameter in rGST-treated group with or without PZQ was associated with decrease in the intralesional L(3)T(4)(+) and increase in Lyt(2)(+) T-cell phenotypes. However, no special relationship was observed between the percentage of resistance and the changes in granuloma diameter or intralesional T-cell phenotypes. The increase in percentage resistance to reinfection was found accompanied by increased anti SWAP IgE. Combined rGST and PZQ provided the complementary goals of improved state of resistance to reinfection 'which was compromized after cure with PZQ' and the maximal reduction in granuloma diameter.
本研究旨在评估重组曼氏血吸虫26谷胱甘肽S-转移酶（rSm 26 GST）或可溶性虫卵抗原（SEA）单独使用以及联合吡喹酮（PZQ）对曼氏血吸虫再感染抵抗状态的影响。同时评估了相关免疫反应的变化。在曼氏血吸虫感染（每只小鼠80条尾蚴）前，对实验组小鼠静脉注射rSm26 GST（1μg×4次）或SEA（10μg×4次），并在感染后6周给予PZQ（2×500mg/kg）。使用了七个对照组，其中三个是感染组（每只小鼠80条尾蚴）、攻击感染组（每只小鼠240条尾蚴）和感染攻击对照组（80 + 240条尾蚴/小鼠）。其余四个组是接受以下处理的对照：相同剂量和时间的GST裂解物、rSmGST、SEA和PZQ。所有组在感染后8周进行攻击感染。攻击感染后3周处死动物。处死动物后进行灌注，并计算对再感染的抵抗百分比。通过测量肝肉芽肿直径、病灶内T细胞表型和血清免疫球蛋白同种型来评估免疫反应。在rGST处理组中观察到对再感染的抵抗百分比最高，而在PZQ处理组中检测到的抵抗百分比最低。而在接受联合rGST或SEA与PZQ的小鼠中，对再感染的抵抗百分比显著高于PZQ处理的小鼠。在rGST处理组中，无论有无PZQ，肉芽肿直径的显著减小都与病灶内L(3)T(4)(+)的减少和Lyt(2)(+) T细胞表型增加有关。然而，在抵抗百分比与肉芽肿直径或病灶内T细胞表型的变化之间未观察到特殊关系。发现对再感染抵抗百分比的增加伴随着抗SWAP IgE的增加。联合rGST和PZQ实现了互补目标，即改善了“经PZQ治愈后受损的”对再感染的抵抗状态，并使肉芽肿直径最大程度减小。
