Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
Toxicol Sci. 2011 Mar;120 Suppl 1:S238-68. doi: 10.1093/toxsci/kfq346. Epub 2010 Nov 22.
The induction by chemicals of allergic sensitization and allergic disease is an important and challenging branch of toxicology. Skin sensitization resulting in allergic contact dermatitis represents the most common manifestation of immunotoxicity in humans, and many hundreds of chemicals have been implicated as skin sensitizers. There are far fewer chemicals that have been shown to cause sensitization of the respiratory tract and asthma, but the issue is no less important because hazard identification remains a significant challenge, and occupational asthma can be fatal. In all areas of chemical allergy, there have been, and remain still, intriguing challenges where progress has required a close and productive alignment between immunology, toxicology, and clinical medicine. What the authors have sought to do here is to exemplify, within the framework of chemical allergy, how an investment in fundamental research and an improved understanding of relevant biological and biochemical mechanisms can pay important dividends in driving new innovations in hazard identification, hazard characterization, and risk assessment. Here we will consider in turn three specific areas of research in chemical allergy: (1) the role of epidermal Langerhans cells in the development of skin sensitization, (2) T lymphocytes and skin sensitization, and (3) sensitization of the respiratory tract. In each area, the aim is to identify what has been achieved and how that progress has impacted on the development of new approaches to toxicological evaluation. Success has been patchy, and there is still much to be achieved, but the journey has been fascinating and there have been some very important developments. The conclusion drawn is that continued investment in research, if coupled with an appetite for translating the fruits of that research into imaginative new tools for toxicology, should continue to better equip us for tackling the important challenges that remain to be addressed.
化学物质诱导过敏致敏和过敏疾病是毒理学的一个重要且具有挑战性的分支。导致过敏接触性皮炎的皮肤致敏反应代表了人类免疫毒性的最常见表现，有数百种化学物质被认为是皮肤致敏剂。能够引起呼吸道致敏和哮喘的化学物质要少得多，但这个问题同样重要，因为危害识别仍然是一个重大挑战，职业性哮喘可能是致命的。在化学过敏的所有领域，都存在着有趣的挑战，而且仍然存在着，这些挑战需要免疫学、毒理学和临床医学之间紧密而富有成效的协作。作者在这里试图在化学过敏的框架内举例说明，在基本研究方面的投资以及对相关生物和生化机制的理解的提高，如何在推动危害识别、危害特征描述和风险评估方面的新创新方面带来重要回报。在这里，我们将依次考虑化学过敏的三个特定研究领域：(1)表皮郎格汉斯细胞在皮肤致敏发展中的作用，(2)T 淋巴细胞与皮肤致敏，以及 (3)呼吸道致敏。在每个领域，目的是确定已经取得了什么成就，以及这些进展如何影响毒理学评估新方法的发展。虽然取得的成功参差不齐，仍有许多工作要做，但这段旅程非常有趣，也有一些非常重要的发展。得出的结论是，如果继续投资于研究，并愿意将研究成果转化为毒理学的富有想象力的新工具，那么应该继续更好地装备我们，以应对仍然存在的重要挑战。
