用于评估潜在免疫调节剂的实验动物模型:综述

Aditya Ganeshpurkar , Ajay K. Saluja
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引用次数: 11

摘要

免疫调节研究的临床前模型是药物发现和开发过程中不可或缺的一部分。尽管如此,它们仍然是人类免疫刺激/抑制的摹本,提供了后者的异质性。本文综述了各种免疫调节研究的临床前模型,即用于免疫调节研究的细胞系,小鼠模型包括体液抗体(HA)反应、延迟型超敏反应、碳清除法巨噬细胞吞噬、对白细胞总数的影响、白细胞动员研究和小鼠致死试验。鱼类模型包括鱼血淋巴细胞吞噬、鱼体内特异性和非特异性反应和肠道细菌定植;而病原体侵染模型包括对蠕形艾美耳球虫的免疫调节。这些生物模型的组合必须作为药物发现过程的特定阶段战略性地加以利用。在选择这种模型时,必须记住,该模型必须与生理学相关。与此同时,它应该能够帮助预测人类的反应。然而,除了“生理学上的相关性”之外,关于试验药物的安全性和有效性的决定性“证据”在于人体研究。尽管如此,对这些模型对人类产生的数据进行合理的解释和设想,以及在临床试验的早期阶段对医学研究的一致重视,对于提高发现新型免疫调节剂的临床研究率是必不可少的。
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Experimental animal models used for evaluation of potential immunomodulators: A mini review

Preclinical models of immunomodulatory studies are indispensable part in the process of drug discovery and development. Still, they are mimeo of human immunostimulation/suppression provided heterogeneity of latter. This review discusses various preclinical models of immunomodulatory studies viz. cell lines for immunomodulatory studies, murine models include humoral antibody (HA) response, delayed type hypersensitivity response, macrophage phagocytosis by carbon clearance method, effect on total leucocytes count, leucocyte mobilization studies, mice lethality test Fish models include phagocytosis by fish blood lymphocytes, specific and non-specific response in fish and intestinal bacterial colonization; whereas pathogen infestation model includes immunomodulation against Eimeria vermiformis.

A portfolio of these biological models has to be utilized strategically as the specific stage of process of drug discovery. During selection of such model it has to be kept in mind that the model must be physiologically relevant. At the same time, it should be able to aid in prediction of human response. Never the less, apart from being ‘physiologically relevant’, the decisive ‘proof’ regarding safety and efficacy of test drugs lies human studies. Still, sensible construal and envision of data resulting from these models to humans, and a conformingly more prominence placed on medical research during early stage of clinical trials, are therefore indispensable to mend on the clinical study rates for discovery of novel immunomodulatory agents.

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