Immunotoxicology Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, North Carolina, USA.
J Immunotoxicol. 2004 Jan;1(1):15-24. doi: 10.1080/15476910490438342.
A number of regulatory agencies in western Europe, Japan and the United States now include guidelines for evaluating the potential immunotoxicity of chemicals, including drugs, as part of routine toxicity testing. Most testing guidelines recommend observational or functional assays that, based on studies in laboratory animals, are able to detect changes in immune function that are associated with increased susceptibility to infectious or neoplastic cell challenge. To appreciate how well observational and functional endpoints are likely to predict an increased risk of infection in humans, it is important to establish correlations between alterations in human immune function and an increased risk of disease. This review will address the clinical evidence for increased risk of disease in humans with mild to moderate levels of immunosuppression using examples from the literature, discuss specific immune system defects associated with increased rates of infection, and examine factors that impact the interpretation of clinical data. The most comprehensive data bases that address these relationships, those derived from patients with primary immunodeficiency and AIDS, are not discussed in this review. These are extreme examples of immunodeficiency and neither the specific clinical diseases that result, nor eventual outcomes, have much in common with that which occurs in individual with chronic mild-to-moderate immunosuppression.
目前，西欧、日本和美国的一些监管机构将评估化学物质（包括药物）免疫毒性的指南纳入常规毒性测试的一部分。大多数测试指南推荐观察性或功能性检测方法，这些方法基于实验室动物研究，能够检测到与感染或肿瘤细胞挑战易感性增加相关的免疫功能变化。为了了解观察性和功能性终点预测人类感染风险增加的程度，重要的是要建立人类免疫功能改变与疾病风险增加之间的相关性。本综述将使用文献中的例子，讨论轻度至中度免疫抑制的人类疾病风险增加的临床证据，讨论与感染率增加相关的特定免疫系统缺陷，并检查影响临床数据解释的因素。本综述没有讨论解决这些关系的最全面的数据基础，这些数据来源于原发性免疫缺陷和艾滋病患者。这些是免疫缺陷的极端例子，由此产生的特定临床疾病及其最终结果与慢性轻度至中度免疫抑制个体的情况并没有太多共同之处。
