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发育免疫毒理学的最新进展及多样效应:第46届美国毒理学会年会(北卡罗来纳州夏洛特)研讨会综述

Recent progress and diverse effects in developmental immunotoxicology: overview of a symposium at the 46th Annual SOT Meeting, Charlotte, NC.

作者信息

Rooney Andrew A, Yang Yung, Makris Susan L

机构信息

National Center for Environmental Assessment, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.

出版信息

J Immunotoxicol. 2008 Oct;5(4):395-400. doi: 10.1080/15476910802481443.

Abstract

It has long been known that the developing immune system is more sensitive and susceptible than the adult immune system to some drugs and environmental contaminants. However, notable advances have been made in the database of studies supporting developmental immunotoxicity (DIT) over the past 5 years. There is considerable evidence that responses of the immune system can be quantitatively or qualitatively different from normal adult responses when xenobiotic exposure occurs during critical periods of immune system development. Qualitative differences of DIT relative to adult exposures include examples of more persistent effects, a latency of effects, and immune dysfunction that is fundamentally different than effects observed when adults are exposed. A symposium was presented at the Society of Toxicology annual meeting to provide an update on advances in the maturing field of developmental immunotoxicology and to facilitate discussion on the range of DIT and later life effects following developmental exposure. In particular, presentations focused on implications of neuroendocrine cross-talk for DIT, the association between developmental air pollutant exposure and asthma, and recent evidence that developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin may increase the risk of autoimmune responses. Several important concepts relative to DIT assessment were illustrated, i.e., (1) Screening for immunosuppression alone is not sufficient to identify all potential immunotoxic effects; (2) DIT cannot be reliably predicted from studies that only utilize adult exposures; (3) Functional testing protocols are preferred in the assessment of DIT; (4) Gender-related differences should be routinely assessed; (5) Latency (i.e., later-life adverse outcomes resulting from developmental exposures) is an important consideration that cannot be detected in adult exposure studies; and, (6) There is increasing support for DIT testing protocols with continuous exposure throughout development until the immune assay is performed.

摘要

长期以来,人们一直知道,发育中的免疫系统比成年免疫系统对某些药物和环境污染物更敏感、更易受影响。然而,在过去5年里,支持发育免疫毒性(DIT)的研究数据库取得了显著进展。有大量证据表明,当在免疫系统发育的关键时期发生外源性物质暴露时,免疫系统的反应在数量或质量上可能与正常成年反应不同。与成年暴露相比,DIT的质量差异包括更持久的影响、影响的潜伏期以及与成年暴露时观察到的影响根本不同的免疫功能障碍。在毒理学会年会上举办了一次研讨会,以介绍发育免疫毒理学这一不断成熟领域的进展,并促进对发育暴露后的DIT范围和晚年影响的讨论。特别是,报告重点关注神经内分泌相互作用对DIT的影响、发育性空气污染物暴露与哮喘之间的关联,以及发育性暴露于2,3,7,8-四氯二苯并对二恶英可能增加自身免疫反应风险的最新证据。阐述了与DIT评估相关的几个重要概念,即:(1)仅筛查免疫抑制不足以识别所有潜在的免疫毒性作用;(2)仅利用成年暴露的研究无法可靠预测DIT;(3)在DIT评估中首选功能测试方案;(4)应常规评估性别相关差异;(5)潜伏期(即发育暴露导致的晚年不良后果)是一个重要考虑因素,在成年暴露研究中无法检测到;(6)越来越多的人支持在整个发育过程中持续暴露直至进行免疫测定的DIT测试方案。

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