Metsärinne K, Forslund T, Teppo A M, Simonsen S, Fyhrquist F
Unit of Clinical Physiology, Minerva Foundation Institute for Medical Research, Helsinki, Finland.
Eur J Med. 1993 Jun-Jul;2(6):333-8.
Interleukin 6 (IL-6) stimulates the production of angiotensinogen (renin substrate, RS), an acute phase reactant and the precursor of the potent vasoconstrictor angiotensin II. This study assesses the effect of cardiac transplantation on plasma levels of angiotensinogen and interleukin 6.
Effects of cardiac transplantation on plasma levels of renin substrate and IL-6 were studied in twelve patients with NYHA IV end-stage heart failure. Renin substrate, IL-6, plasma renin activity, C-reactive protein and serum amyloid A were determined 1 day before cardiac transplantation, and 1 day, 1 week, 4 weeks and 12 weeks postoperatively. Renin substrate was measured by both direct and indirect radioimmunoassay. An indirect assay measures intact renin substrate only, capable of releasing angiotensin I, while a direct assay measures both intact renin substrate and des-angiotensin I-renin substrate, the residue of renin substrate after cleavage of angiotensin I.
Plasma renin substrate and IL-6 increased significantly on day 1 as compared with preoperative levels. Plasma renin substrate increased (measured by direct and indirect assay) by 64 and 50%, respectively, IL-6 levels by 43%. Plasma IL-6 returned to preoperative (normal) levels by 4-12 weeks. Plasma renin substrate levels remained elevated for the follow-up period of 12 weeks. The direct assay always gave higher values than the indirect assay, presumably due to consumption of renin substrate by renin. Consequently, a negative correlation between plasma renin activity and renin substrate measured with indirect assay was observed.
Our findings suggest that cardiac transplantation brings about an acute phase reaction, mediated partly by IL-6, with increased synthesis of acute phase proteins like renin substrate. This may result in increased angiotensin II levels. Considering the trophic effects of angiotensin II on vascular tissue, increased production of renin substrate may contribute to the development of proliferative cardiovascular changes in heart transplant recipients.
白细胞介素6（IL-6）可刺激血管紧张素原（肾素底物，RS）的产生，血管紧张素原是一种急性期反应物，也是强效血管收缩剂血管紧张素II的前体。本研究评估心脏移植对血管紧张素原和白细胞介素6血浆水平的影响。
在12例纽约心脏协会（NYHA）心功能IV级的终末期心力衰竭患者中，研究心脏移植对肾素底物和IL-6血浆水平的影响。在心脏移植前1天以及术后1天、1周、4周和12周测定肾素底物、IL-6、血浆肾素活性、C反应蛋白和血清淀粉样蛋白A。肾素底物通过直接和间接放射免疫测定法进行测量。间接测定法仅测量能够释放血管紧张素I的完整肾素底物，而直接测定法测量完整肾素底物和去血管紧张素I-肾素底物，后者是血管紧张素I裂解后肾素底物的残余物。
与术前水平相比，第1天血浆肾素底物和IL-6显著升高。血浆肾素底物（通过直接和间接测定法测量）分别升高了64%和50%，IL-6水平升高了43%。血浆IL-6在4 - 12周时恢复到术前（正常）水平。血浆肾素底物水平在12周的随访期内一直保持升高。直接测定法得出的值总是高于间接测定法，这可能是由于肾素消耗了肾素底物。因此，观察到血浆肾素活性与间接测定法测量的肾素底物之间呈负相关。
我们的研究结果表明，心脏移植引发了一种急性期反应，部分由IL-6介导，导致肾素底物等急性期蛋白的合成增加。这可能导致血管紧张素II水平升高。考虑到血管紧张素II对血管组织的营养作用，肾素底物产生的增加可能有助于心脏移植受者发生增殖性心血管变化。
