C-反应蛋白（C-reactive protein，CRP）作为敏感的炎症标志物被广泛认可。血浆/血清CRP水平升高与疾病状态的关联备受关注，尽管CRP并非某一特定疾病状态的特异性指标。监测血液中的CRP水平以评估疾病严重程度、预测疾病进展和预后取得了不同程度的成功。高CRP水平被认为是识别心血管疾病和某些癌症患者风险以及指导治疗的有用标志，但其作用与上下文有关。由于即使强关联也不能建立因果关系，CRP的病原作用经常被过度解释。CRP作为生物体对细菌感染、组织损伤和自身免疫的重要调节因子发挥作用。CRP存在构象上不同的形式，各具不同的功能特性，有助于解释CRP所具有的多样且常常矛盾的效应。特别是，原生五聚体CRP解离为其亚单位单体CRP后，揭示了五聚体CRP中“隐藏”的促炎活性。在这里，我们回顾了CRP靶向策略、治疗降低循环CRP水平和CRP拮抗剂以及构象变化抑制剂的开发近期进展。我们还将讨论它们在减轻CRP在心血管、肺部、自身免疫疾病和癌症等各种病理情况下的有害作用方面的治疗潜力。版权所有 © 2023 Rizo-Téllez、Sekheri和Filep。

C-reactive protein (CRP) is well-recognized as a sensitive biomarker of inflammation. Association of elevations in plasma/serum CRP level with disease state has received considerable attention, even though CRP is not a specific indicator of a single disease state. Circulating CRP levels have been monitored with a varying degree of success to gauge disease severity or to predict disease progression and outcome. Elevations in CRP level have been implicated as a useful marker to identify patients at risk for cardiovascular disease and certain cancers, and to guide therapy in a context-dependent manner. Since even strong associations do not establish causality, the pathogenic role of CRP has often been over-interpreted. CRP functions as an important modulator of host defense against bacterial infection, tissue injury and autoimmunity. CRP exists in conformationally distinct forms, which exhibit distinct functional properties and help explaining the diverse, often contradictory effects attributed to CRP. In particular, dissociation of native pentameric CRP into its subunits, monomeric CRP, unmasks "hidden" pro-inflammatory activities in pentameric CRP. Here, we review recent advances in CRP targeting strategies, therapeutic lowering of circulating CRP level and development of CRP antagonists, and a conformation change inhibitor in particular. We will also discuss their therapeutic potential in mitigating the deleterious actions attributed to CRP under various pathologies, including cardiovascular, pulmonary and autoimmune diseases and cancer.Copyright © 2023 Rizo-Téllez, Sekheri and Filep.