Department of Immunology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
Center for Drug Safety Evaluation and Research, School of Pharmacy, Zhejiang University, Hangzhou, China.
PLoS Negl Trop Dis. 2021 Nov 24;15(11):e0009927. doi: 10.1371/journal.pntd.0009927. eCollection 2021 Nov.
The metacestode stage of Echinococcus granulosus can cause cystic echinococcosis (CE), which still widely occurs around the world. Since the early 1970s, benzimidazoles have been shown to inhibit the growth of cysts and used to treat CE. However, benzimidazoles are still ineffective in 20%-40% of cases. In order to explore the new agents against CE, we have investigated the therapeutic effect of the recombinant adenoviral vector expressing mouse IL-28B (rAd-mIL-28B) on protoscoleces-infected mice. In our study, we successfully established the model mice which infected with protoscoleces intraperitoneally. At 18 weeks post-infection, the mice received rAd-mIL-28B (1×107 PFU) weekly by intramuscular injection for 6 weeks. Compared with the untreated control (13.1 ± 2.2 g), there was a significant reduction in cysts wet weight in rAd-mIL-28B group (8.3 ± 3.5 g) (P < 0.05), especially in Albendazole (ABZ) + rAd-mIL-28B group (5.8 ± 1.4 g) (P < 0.01). We also observed the severe damage of the germinal layer and the laminated layer of cysts after treatment. rAd-mIL-28B group showed a prominent increase in the level of Th1 type cytokines (such as IFN-γ, IL-2 and TNF-α). Meanwhile, the frequency of Foxp3+ T cells was decreased in the rAd-mIL-28B group (4.83 ± 0.81%) and ABZ + rAd-mIL-28B group (4.60 ± 0.51%), comparing with the untreated group (8.13 ± 2.60%) (P < 0.05). In addition, compared with the untreated control (122.14 ± 81.09 pg/ml), the level of IFN-γ significantly increased in peritoneal fluid in the rAd-mIL-28B group (628.87 ± 467.16 pg/ml) (P < 0.05) and ABZ + rAd-mIL-28B group (999.76 ± 587.60 pg/ml) (P < 0.001). Taken together, it suggested that ABZ + IL-28B may be a potential therapeutic agent against CE.
细粒棘球蚴的囊尾蚴期可引起包虫病(CE),该病仍广泛发生于世界各地。自 20 世纪 70 年代早期以来,已证明苯并咪唑类药物可抑制囊肿生长并用于治疗 CE。然而,苯并咪唑类药物在 20%-40%的病例中仍然无效。为了探索治疗 CE 的新药物,我们研究了表达小鼠白细胞介素 28B 的重组腺病毒载体(rAd-mIL-28B)对原头蚴感染小鼠的治疗效果。在本研究中,我们成功地建立了经腹腔感染原头蚴的模型小鼠。感染后 18 周,每周通过肌肉注射 rAd-mIL-28B(1×107PFU)6 周。与未治疗对照组(13.1 ± 2.2g)相比,rAd-mIL-28B 组囊蚴湿重显著减轻(8.3 ± 3.5g)(P<0.05),尤其是阿苯达唑(ABZ)+rAd-mIL-28B 组(5.8 ± 1.4g)(P<0.01)。我们还观察到治疗后囊蚴的生发层和层状层严重受损。rAd-mIL-28B 组 Th1 型细胞因子(如 IFN-γ、IL-2 和 TNF-α)水平显著升高。同时,rAd-mIL-28B 组(4.83 ± 0.81%)和 ABZ+rAd-mIL-28B 组(4.60 ± 0.51%)的 Foxp3+T 细胞频率均低于未治疗组(8.13 ± 2.60%)(P<0.05)。此外,与未治疗对照组(122.14 ± 81.09pg/ml)相比,rAd-mIL-28B 组腹腔液中 IFN-γ 水平显著升高(628.87 ± 467.16pg/ml)(P<0.05)和 ABZ+rAd-mIL-28B 组(999.76 ± 587.60pg/ml)(P<0.001)。综上所述,ABZ+IL-28B 可能是治疗 CE 的潜在药物。