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首页> 外文期刊>Human and Experimental Toxicology >Carcinogenicity testing of IL-10: principles and practicalities.
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Carcinogenicity testing of IL-10: principles and practicalities.

机译：IL-10致癌性测试：原理和实用性。

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摘要

IL-10 is a cytokine with actions at many levels of the immune system. In the course of development of recombinant human IL-10 (rhuIL-10) as a potential treatment for a number of chronic diseases of man, the question 'What about its carcinogenicity testing?' was repeatedly asked, based on scientific evaluation by toxicologists, beliefs about regulatory requirements, and questions considered likely to be raised by physicians, patients, and lawyers. The feasibility of various approaches to the carcinogenicity testing of rhuIL-10 is critically discussed here as a contribution to rational consideration of the general need for and value of such testing, and its particular feasibility for a recombinant human protein with profound effects on the immune system. The physiological functions of IL-10 in man and rodents are reviewed in detail, as there are notable differences between species in its normal activities, followed by detailed evaluation of the potential procedures and practical problems of its carcinogenicity testing as a heterologous, immunogenic protein in rodents. The value of information that might be obtained from transgenic mice is also evaluated, and so are the results of studies exploring its actions on human tumour cell biopsies and rodent and human cell lines. It is concluded that despite the probable popular and regulatory expectations that carcinogenicity test results would be provided, all the physiological and pathological information reveals no indication that rhuIL-10 would pose a carcinogenic risk to humans on prolonged administration, and that it would not be feasible to undertake such experimentation. It is argued that in this, as in other instances, professional and popular expectations have run beyond practical feasibility or theoretical justification. Cautious and critical evaluation should be made every time shorter or longer term toxicity studies of any candidate drug are planned or even considered, especially if it is a recombinant protein, to decide on objective grounds whether the studies are really necessary and whether they can be done in a way that will give meaningful results that will help in risk assessment.
机译：IL-10是一种在多种免疫系统水平上都有作用的细胞因子。在开发重组人IL-10（rhuIL-10）作为治疗多种人类慢性疾病的潜在方法的过程中，问题“其致癌性测试如何？”根据毒理学家的科学评估，对法规要求的信念以及医师，患者和律师可能提出的问题，反复询问。本文对rhuIL-10致癌性测试的各种方法的可行性进行了重点讨论，以帮助合理考虑此类测试的一般需求和价值，以及其对于对免疫系统产生深远影响的重组人蛋白质的特殊可行性。 。对IL-10在人和啮齿动物中的生理功能进行了详细的综述，因为物种之间在其正常活动方面存在显着差异，然后详细评估了其作为异源免疫原性蛋白的潜在致癌性测试的程序和实际问题。啮齿动物。还评估了可能从转基因小鼠中获得的信息的价值，并探讨了其对人类肿瘤细胞活检以及啮齿动物和人类细胞系的作用的研究结果。结论是，尽管可能会提供致癌性测试结果，但所有的生理和病理学信息均未显示出rhuIL-10长期服用会对人类构成致癌危险的迹象，因此这是不可行的。进行这样的实验。有人认为，在这种情况下，与其他情况一样，专业和公众的期望超出了实际可行性或理论依据。每当计划或什至考虑对任何候选药物进行短期或长期毒性研究（尤其是重组蛋白质）时，都应进行谨慎而严格的评估，以客观地确定研究是否确实必要以及是否可以进行研究以产生有意义的结果的方式来帮助进行风险评估。

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