Immunomodulatory treatment with thalidomide in experimental leptospirosis in Golden Syrian hamsters (Mesocricetus auratus)

Immunomodulatory treatment with thalidomide in experimental leptospirosis in Golden Syrian hamsters (Mesocricetus auratus)
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DOI:
10.1093/trstmh/trt112
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发表时间:
2014-02-01
影响因子:
2.2
通讯作者:
Athanazio, Daniel Abensur
Athanazio, Daniel Abensur
中科院分区:
医学4区
文献类型:
--
作者:
Soares, Luciane Marieta;Macedo, Julio Oliveira;Athanazio, Daniel Abensur

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背景:钩端螺旋体病在症状出现4天后开始治疗,抗生素的疗效有限,迫切需要新的辅助治疗方案。方法:用问号钩端螺旋体L1-130株感染金黄地鼠,按不治疗(无治疗)、沙利度胺(TAL)、氨苄西林(AMP)或两者兼用(AMP-TAL)进行分组。实验1:AMP组和AMP-TAL组的仓鼠全部存活(n=8),而None组(n=6)和TAL组(n=8)的仓鼠全部死亡。AMP组和AMP-TAL组无肾或肝病理改变,靶器官无钩端螺旋体负荷或极低。实验2:无组6只仓鼠中有6只死亡,TAL组8只仓鼠死亡,AMP和AMP-TAL组均有6只仓鼠死亡。与单独使用氨苄西林治疗的仓鼠相比,沙利度胺没有显示出生存益处。结论:沙利度胺对钩端螺旋体病金黄地鼠模型晚期治疗的存活率影响很小。
Background: The benefit of antibiotics in leptospirosis is limited when treatment is started four days after symptoms appear, and new adjuvant therapeutic options are urgently needed.Methods: Hamsters (Mesocricetus auratus) were infected by Leptospira interrogans strain L1-130, and groups were assigned based on no treatment (NONE), thalidomide only (TAL), ampicillin only (AMP) or both (AMP-TAL). Treatment was started two days after the onset of symptoms (experiment 1) and immediately after detection of the first death (experiment 2).Results: Experiment 1: all hamsters from the groups AMP and AMP-TAL survived (n=8), while all hamsters from groups NONE (n=6) and TAL (n=8) died. The AMP and the AMP-TAL groups showed no renal or liver pathology and absent or very low leptospiral burden in target organs. Experiment 2: lethal outcome was observed in 6/6 hamsters in the NONE group, 8/8 in the TAL group, and 6/8 in both the AMP and AMP-TAL groups. Thalidomide showed no survival benefit when compared to hamsters treated with ampicillin alone. The TAL, AMP and AMP-TAL groups had very low tissue leptospiral counts.Conclusion: Thalidomide had minimal impact on survival in the late treatment of leptospirosis hamster model.