Effect of biotherapeutics on cyclosporin-induced Clostridium difficile infection in mice
Effect of biotherapeutics on cyclosporin-induced Clostridium difficile infection in mice
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DOI：
10.1111/j.1440-1746.2009.06135.x
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发表时间：
2010-04-01
影响因子：
4.1
通讯作者：
Prasad, Kaushal Kishor
中科院分区：
文献类型：
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作者：
Kaur, Sukhminderjit;Vaishnavi, Chetana;Prasad, Kaushal Kishor
背景和目的：免疫抑制治疗可诱发艰难梭菌相关疾病（CDAD）。本研究采用小鼠实验性CDAD模型，观察环孢素（CsA）在CDAD发病中的作用，并观察益生菌和表皮生长因子（EGF）对CDAD的生物治疗作用。未给予任何接种物的第I组动物作为对照。其余三组（组II、III和IV）的动物从第1-7天每天给予环孢菌素，随后给予C。艰难梭菌接种物。此外，动物在C后接受嗜酸乳杆菌（组III）和EGF（组IV）一周。艰难的挑战对动物进行C.结果：艰难梭菌在接受环孢素和C.很难盲肠和结肠组织中MPO活性显著升高（P < 0.05），并出现上皮细胞损伤、隐窝炎和急性炎症改变。C.在接受益生菌和EGF的动物中，艰难梭菌计数、毒素A和B滴度以及MPO活性显著降低（P < 0.05）。组织学上，mucodepletion和炎性浸润减少在biobirons接收animals.Conclusions：环孢素导致的发展轻至中度CDAD的动物。生物治疗剂的施用降低了CDAD的严重程度。未来的临床试验需要进一步研究这些潜在的生物学指标。
Background and Aim:Immunosuppressive therapy may precipitate Clostridium difficile associated disease (CDAD). We evaluated the role of cyclosporin in the development of CDAD in the experimental mouse model and studied the effect of probiotic and epidermal growth factor (EGF) as biotherapeutics measures.Methods:BALB/c mice (n = 24) were divided into four groups. Group I animals not given any inoculum served as controls. Animals in the remaining three groups (Group II, III and IV) were given cyclosporin daily from days 1-7 followed by C. difficile inoculum on day 8. Additionally, the animals received Lactobacillus acidophilus (Group III) and EGF (Group IV) for one-week post C. difficile challenge. The animals were evaluated for colonization and toxin production by C. difficile, myeloperoxidase (MPO) activity and histopathological changes.Results:Clostridium difficile was colonized and elaborated its toxins in animals receiving cyclosporin and C. difficile. MPO activity was significantly higher (P < 0.05) and histopathological epithelial damage, cryptitis and acute inflammatory changes were seen in the cecum and colon. C. difficile count, toxins A and B titers and MPO activity were significantly lowered (P < 0.05) in animals receiving probiotic and EGF. Histopathologically, mucodepletion and inflammatory infiltrate were decreased in the biotherapeutic receiving animals.Conclusions:Cyclosporin led to the development of mild to moderate CDAD in animals. Administration of biotherapeutics reduced the severity of CDAD. Future clinical trials are needed for further investigation of these potential biotherapeutic measures.