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首页> 外文期刊>Current Immunology Reviews >From the Obscure and Mysterious Acute Phase Response to Toll-Like Receptors and the Cytokine Network
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From the Obscure and Mysterious Acute Phase Response to Toll-Like Receptors and the Cytokine Network

机译：从模糊和神秘的急性期反应到收费受体和细胞因子网络。

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The discovery of C-reactive protein (CRP) almost 80 years ago in the blood of patients with various infectiousnand inflammatory diseases initiated studies on the mysterious biological phenomenon called “the acute phase response”n(APR). The complex metabolic alterations accompanying APR include changes in the plasma concentration of the majoritynof liver-produced proteins – acute phase proteins (APPs). The search for mediators released from the site of injury andnable to stimulate hepatocytes led to the discovery of “Leukocytic Endogenous Mediator” (or “Endogenous Pyrogen”), initiallynidentified with interleukin-1. Only in 1987 was the main factor able to induce the majority of symptoms of APR discoverednand named interleukin-6 (IL-6). The current paradigm assumes that APR is elicited by numerous proinflammatoryncytokines, the principal role being played by the IL-6-family. The last decade has brought about significantnprogress in understanding the initiation of the acute phase response (recognition of pathogens by Toll-like receptors), interactionnof cytokines and their receptors (origin and importance of soluble cytokine receptors, construction of hypercytokinesnby protein fusion), the mechanism of multi-step signal transduction from the plasma membrane to nuclear transcriptionnfactors (including the role of MAP kinases), as well as elucidation of the role of receptor cross-talk in cytokinennetworks in health and disease. Genomic techniques indicate that hundreds of genes participate in the development ofnAPR. The data presented here emphasize the growing importance of APR for clinical medicine and confirm the close relationshipnbetween acute phase response and innate immunity.
机译：大约80年前，在患有各种传染性和炎性疾病的患者的血液中发现了C反应蛋白（CRP），从而开始了对被称为“急性期反应”（APR）的神秘生物学现象的研究。伴随APR的复杂代谢变化包括肝脏产生的大多数蛋白质-急性期蛋白质（APPs）的血浆浓度变化。寻找从损伤部位释放并能刺激肝细胞的介体导致发现“白细胞内源性介体”（或“内源性热原”），最初被白介素-1识别。直到1987年，才被发现能够诱导大多数APR症状的主要因素，并被称为白细胞介素6（IL-6）。当前的范例假定APR是由多种促炎性细胞因子引起的，IL-6家族起主要作用。在过去的十年中，在理解急性期反应的开始（通过Toll样受体识别病原体），细胞因子及其受体的相互作用（可溶性细胞因子受体的起源和重要性，通过蛋白融合构建高细胞因子）方面取得了重大进展。从质膜到核转录因子的多步信号转导（包括MAP激酶的作用），以及阐明健康和疾病中细胞因子网络中受体串扰的作用。基因组技术表明数百种基因参与nAPR的发展。本文提供的数据强调了APR在临床医学中的重要性，并证实了急性期反应与先天免疫之间的密切关系。

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