Therapeutic Lowering of C-Reactive Protein.

Therapeutic Lowering of C-Reactive Protein.
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DOI:
10.3389/fimmu.2020.619564
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发表时间:
2020
影响因子:
7.3
通讯作者:
Szalai AJ
Szalai AJ
中科院分区:
医学2区
文献类型:
--
作者:
Jimenez RV;Szalai AJ

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在健康个体的血液中,C - 反应蛋白(CRP)通常含量极低,然而,在因创伤以及感染性和非感染性疾病相关的组织损伤和炎症反应时,其血液浓度会大幅且迅速升高。因此,住院患者的CRP血浆或血清水平通常会受到监测,以评估其初始疾病和损伤的严重程度,以及后续对治疗的反应和恢复健康的情况。尽管它作为炎症的可靠指标具有临床实用性,但人们常常错误地认为,只有当血液中CRP升高时,CRP的生物学作用(无论其作用为何)才会显现。事实上,在过去几十年中,对人类和动物(例如人CRP转基因小鼠和CRP基因敲除小鼠)的研究表明,即使在血液没有显著升高的情况下,即便是在基线水平,CRP也是生物活性的重要介质。在这篇综述中,我们简要回顾了CRP的历史,包括对其发现、早期临床应用以及在基线水平和急性期反应期间的生物合成的描述。接下来,我们概述了我们及其他人利用关节炎、新生内膜增生和急性肾损伤动物模型所获得的证据,这些证据表明基线水平的CRP具有重要的生物学效应。最后,我们讨论了通过治疗降低基线CRP水平可能是治疗某些疾病(包括癌症)的一种有用方法的可能性。
In the blood of healthy individuals C-reactive protein (CRP) is typically quite scarce, whereas its blood concentration can rise robustly and rapidly in response to tissue damage and inflammation associated with trauma and infectious and non-infectious diseases. Consequently, CRP plasma or serum levels are routinely monitored in inpatients to gauge the severity of their initial illness and injury and their subsequent response to therapy and return to health. Its clinical utility as a faithful barometer of inflammation notwithstanding, it is often wrongly concluded that the biological actions of CRP (whatever they may be) are manifested only when blood CRP is elevated. In fact over the last decades, studies done in humans and animals (e.g. human CRP transgenic and CRP knockout mice) have shown that CRP is an important mediator of biological activities even in the absence of significant blood elevation, i.e. even at baseline levels. In this review we briefly recap the history of CRP, including a description of its discovery, early clinical use, and biosynthesis at baseline and during the acute phase response. Next we overview evidence that we and others have generated using animal models of arthritis, neointimal hyperplasia, and acute kidney injury that baseline CRP exerts important biological effects. In closing we discuss the possibility that therapeutic lowering of baseline CRP might be a useful way to treat certain diseases, including cancer.
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