From the Wolfson Drug Discovery Unit, and the National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, University College London, London, United Kingdom (M.B.P., T.L., H.J.L., J.D.G., P.N.H.); Department of Clinical Biochemistry, Royal Free Hospital, London, United Kingdom (N.W.); and the National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, United Kingdom (S.P., Y.M.).
Circ Res. 2014 Feb 14;114(4):672-6. doi: 10.1161/CIRCRESAHA.114.302770. Epub 2013 Dec 12.
Baseline circulating concentrations of C-reactive protein (CRP) are significantly associated with cardiovascular disease risk in general populations. This modest association has been inappropriately conflated with causality, and it has been claimed that CRP is proatherogenic. Most of the known causative factors for atherosclerosis stimulate increased CRP production, but comprehensive genetic epidemiology studies provide no support for a pathogenic role of CRP. The reported proinflammatory effects of human CRP preparations on healthy cells in vitro and in healthy animals in vivo have all been produced by poorly characterized CRP preparations, demonstrably caused by impurities, or elicited by CRP made in recombinant Escherichia coli not by humans. None of the in vitro or animal findings have been reproduced with pure natural human CRP. Nevertheless, the strong proinflammatory effects of infusing recombinant bacterial CRP into humans have still been inappropriately ascribed to CRP.
To investigate the effects of infusion into healthy adult human volunteers of pure natural human CRP.
Comprehensively characterized, pharmaceutical-grade, endotoxin-free, purified CRP, prepared to GMP standard from pooled normal human donor plasma was infused as an intravenous bolus in 7 healthy adult human volunteers at ≤2 mg/kg to provide circulating CRP concentrations ≤44 mg/L. No recipient showed any significant clinical, hematologic, coagulation, or biochemical changes, or any increase in proinflammatory cytokines or acute phase proteins.
The human CRP molecule itself is not proinflammatory in healthy human adults.
在一般人群中，基线循环 C 反应蛋白（CRP）浓度与心血管疾病风险显著相关。这种适度的关联被不适当地与因果关系混淆，并且有人声称 CRP 是促动脉粥样硬化的。大多数已知的动脉粥样硬化致病因素刺激 CRP 的产生增加，但综合遗传流行病学研究并未提供 CRP 致病作用的支持。据报道，CRP 制剂对健康细胞的体外和健康动物的体内的促炎作用均由特征不明确的 CRP 制剂产生，这些制剂显然是由杂质引起的，或者是由重组大肠杆菌而不是人类产生的 CRP 引起的。在体外或动物实验中均未用纯天然 CRP 制剂复制这些发现。然而，将重组细菌 CRP 输注到人体中所产生的强烈促炎作用仍被不适当地归因于 CRP。
研究输注纯天然人 CRP 对健康成年人体志愿者的影响。
采用综合特征描述、药物级、无内毒素、GMP 标准制备的、从正常人类供体血浆中混合制备的纯化 CRP，以静脉推注方式输注至 7 名健康成年人体志愿者，剂量≤2mg/kg，以提供循环 CRP 浓度≤44mg/L。没有受者出现任何显著的临床、血液学、凝血或生化变化，或任何促炎细胞因子或急性期蛋白的增加。
CRP 分子本身在健康的成年人体内没有促炎作用。
