Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/Fundación de Investigaciones Biomédicas de Córdoba (FIBICO), Córdoba, Spain.
Nephrol Dial Transplant. 2012 Jul;27(7):2907-12. doi: 10.1093/ndt/gfr767. Epub 2012 Jan 13.
The principal cause of mortality in haemodialysis (HD) patients is cardiovascular disease, which is linked to chronic inflammation. Recent studies have demonstrated that angiotensin II receptor AT1 antagonists have anti-inflammatory properties. In this study, we evaluated the effect of losartan on CD14+CD16+ monocytes in HD patients. In addition, we developed an in vitro model to study the mechanisms by which losartan modulates these cells.
We divided 18 HD patients into two groups, based on anti-hypertensive treatment: 9 patients were treated with losartan (losartan group) and 9 received other anti-hypertensive drugs that did not affect the renin-angiotensin axis (no-losartan group). Losartan was withdrawn in five patients from the losartan group for 2 months. Ten healthy subjects were included as controls. Invitro, we studied the differentiation of monocytes from healthy donors on stimulation with interleukin (IL)-10, IL-4 and granulocyte monocytes colony-stimulating factor with or without losartan in the culture medium.
In patients who were taking losartan, the percentage of monocytes that expressed CD14+CD16+ was lower compared with patients in the no-losartan group. The percentage of CD14+CD16+ was similar in the losartan group and healthy subjects. When losartan was withdrawn from five patients in the losartan group, the percentage of CD14+CD16+ monocytes increased compared with before withdrawal. In vitro, when we added losartan to the culture medium, CD14++CD16- monocytes failed to differentiate into CD14+CD16+ cells.
Losartan acts as an immunomodulator that prevents the development of CD14+CD16+ pro-inflammatory monocytes in HD patients.
血液透析（HD）患者的主要死亡原因是心血管疾病，这与慢性炎症有关。最近的研究表明，血管紧张素 II 受体 AT1 拮抗剂具有抗炎特性。在这项研究中，我们评估了氯沙坦对 HD 患者 CD14+CD16+单核细胞的影响。此外，我们建立了体外模型来研究氯沙坦调节这些细胞的机制。
我们根据抗高血压治疗将 18 名 HD 患者分为两组：9 名患者接受氯沙坦（氯沙坦组）治疗，9 名患者接受不影响肾素-血管紧张素轴的其他抗高血压药物（非氯沙坦组）治疗。氯沙坦组中有 5 名患者停用氯沙坦 2 个月。10 名健康受试者作为对照。我们在体外研究了健康供体的单核细胞在白细胞介素（IL）-10、IL-4 和粒细胞单核细胞集落刺激因子刺激下分化的情况，以及有无氯沙坦在培养基中的情况。
服用氯沙坦的患者中表达 CD14+CD16+的单核细胞比例低于未服用氯沙坦的患者。氯沙坦组与健康受试者的 CD14+CD16+比例相似。当氯沙坦组的 5 名患者停用氯沙坦时，与停药前相比，CD14+CD16+单核细胞的比例增加。在体外，当我们将氯沙坦添加到培养基中时，CD14++CD16-单核细胞未能分化为 CD14+CD16+细胞。
氯沙坦作为一种免疫调节剂，可防止 HD 患者中 CD14+CD16+促炎单核细胞的发展。
