Liu Andrew H
Division of Pediatric Allergy and Immunology, National Jewish Medical and Research Center, and the Department of Pediatrics, University of Colorado Health Sciences Center, Denver 80206, USA.
J Allergy Clin Immunol. 2002 Mar;109(3):379-92. doi: 10.1067/mai.2002.122157.
Well-established evidence links endotoxin exposure, especially in the workplace, to airways disease. Endotoxin can increase disease severity by acting as a natural adjuvant to augment asthma and atopic inflammation. Recent studies suggest that it can even act on its own, causing a distinct endotoxic form of asthma. Other studies, however, contradict the paradigm that endotoxin's influence is solely a negative one. Epidemiologic associations of environmental endotoxin exposure with allergy and asthma prevention are consistent with hygiene hypothesis associations of other microbial exposures or infections with a lower incidence of atopic disease. Currently, microbe-derived products are being developed as potential therapies for allergy and asthma. Thus it is an ideal time to consider endotoxin as a prototype of a natural intervention with microbial components. Nature's ongoing experiment with endotoxin can provide clues for the development of effective and safe microbe-based products for disease treatment and prevention. This article will discuss (1) conventional paradigms in which endotoxin-induced immune modulation by T(H)1-type induction leads to mitigation of T(H)2-type immune development, allergen sensitization, and atopic inflammation; (2) newer concepts of T(H)1-type immune responses that may provide additional asthma-protective effects by preventing airways remodeling; (3) home and environmental features that significantly contribute to endotoxin exposure; (4) different aspects of asthma mediated by endotoxin exposure; and (5) how to understand endotoxin's paradoxical nature of serving as both friend and foe.
充分的确凿证据表明，接触内毒素，尤其是在工作场所接触内毒素，与气道疾病有关。内毒素可作为一种天然佐剂增强哮喘和特应性炎症，从而加重疾病的严重程度。最近的研究表明，它甚至可以独立发挥作用，引发一种独特的内毒素性哮喘。然而，其他研究与内毒素的影响完全是负面的这一范式相矛盾。环境内毒素暴露与过敏和哮喘预防之间的流行病学关联，与其他微生物暴露或感染与较低特应性疾病发病率的卫生假说关联是一致的。目前，微生物衍生产品正在被开发为治疗过敏和哮喘的潜在疗法。因此，现在是将内毒素视为一种含有微生物成分的天然干预原型的理想时机。大自然对内毒素的持续“实验”可为开发有效且安全的基于微生物的疾病治疗和预防产品提供线索。本文将讨论：（1）传统范式，即内毒素通过诱导T(H)1型免疫调节来减轻T(H)2型免疫发育、变应原致敏和特应性炎症；（2）T(H)1型免疫反应的新概念，该概念可能通过防止气道重塑提供额外的哮喘保护作用；（3）对室内和环境中内毒素暴露有显著影响的因素；（4）内毒素暴露介导的哮喘的不同方面；以及（5）如何理解内毒素亦敌亦友的矛盾性质。
