Burger Danielle, Dayer Jean-Michel
Division of Immunology and Allergy (Hans Wilsdorf Laboratory), Department of Internal Medicine, University Hospital, 24 rue Micheli-du-Crest, 1211 Geneva 14, Switzerland.
Autoimmun Rev. 2002 Feb;1(1-2):111-7. doi: 10.1016/s1568-9972(01)00018-0.
The etiology of chronic immuno-inflammatory diseases including rheumatoid arthritis (RA), multiple sclerosis (MS), systemic lupus erythematosus (SLE), and atherosclerosis is far from being elucidated. It is generally accepted that multiple factors are involved in the development of such pathologies, including factors of genetic susceptibility that interact in complex ways with diverse environmental factors, i.e. gender, nutrition, environment, etc. Furthermore, infection has often been pinpointed as playing a causal role. However, no distinctive pattern has yet emerged from the tremendous number of compiled results that would provide a generally acceptable hypothesis of the etiology of immuno-inflammatory diseases, and the possibility of a persistent antigenic stimulus arising from an infection cannot be confirmed or refuted. At the cellular level, chronic inflammation is characterized by the infiltration of immuno-inflammatory cells into the target tissue, which mostly precedes tissue damage. At the inflammatory site, monocytes and T lymphocytes are in close proximity. We have demonstrated that contact-mediated activation of monocytes by stimulated T lymphocytes is a major stimulus triggering the production of large amounts of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) whose importance in chronic inflammation is well known. We recently established that high-density lipolipoprotein (HDL)-associated apolipoprotein (apo) A-I is a specific inhibitor of cytokine production in monocyte-macrophages upon contact with stimulated T cells. HDL-associated apo A-I is a negative acute-phase protein, i.e. a protein whose level is lowered by more than 25% during the acute phase. This review aims at highlighting the fact that HDL-associated apo A-I might play the role of a constitutive anti-inflammatory factor. The decrease of plasma levels of HDL-associated apo A-I upon acute inflammation may be a sign of the possible development of chronic inflammation, i.e. individuals presenting with risk factors might develop chronic inflammatory diseases after infection. We thus hypothesize that HDL-associated apo A-I might be the missing link between infection and chronic inflammation.
包括类风湿性关节炎（RA）、多发性硬化症（MS）、系统性红斑狼疮（SLE）和动脉粥样硬化在内的慢性免疫炎症性疾病的病因远未阐明。人们普遍认为，多种因素参与了此类疾病的发展，包括遗传易感性因素，这些因素与多种环境因素（如性别、营养、环境等）以复杂的方式相互作用。此外，感染常常被认为起着因果作用。然而，从大量已汇总的结果中尚未出现一种独特的模式，能够提供一个被普遍接受的免疫炎症性疾病病因假说，并且感染引发持续抗原刺激的可能性既无法得到证实，也无法被反驳。在细胞水平上，慢性炎症的特征是免疫炎症细胞浸润到靶组织中，这大多先于组织损伤。在炎症部位，单核细胞和T淋巴细胞紧密相邻。我们已经证明，受刺激的T淋巴细胞通过接触介导激活单核细胞是触发大量肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）产生的主要刺激因素，它们在慢性炎症中的重要性是众所周知的。我们最近发现，高密度脂蛋白（HDL）相关载脂蛋白（apo）A-I是单核巨噬细胞在与受刺激的T细胞接触时细胞因子产生的特异性抑制剂。HDL相关apo A-I是一种负急性期蛋白，即在急性期其水平降低超过25%的一种蛋白质。本综述旨在强调HDL相关apo A-I可能发挥组成性抗炎因子作用这一事实。急性炎症时HDL相关apo A-I血浆水平的降低可能是慢性炎症可能发展的一个迹象，即有风险因素的个体在感染后可能发展为慢性炎症性疾病。因此，我们假设HDL相关apo A-I可能是感染与慢性炎症之间缺失的环节。
