Losartan prevents the development of the pro-inflammatory monocytes CD14+CD16+ in haemodialysis patients

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2012-07, Vol.27 (7), p.2907-2912
• Main Authors: MERINO, Ana, ALVAREZ-LARA, Maria Antonia, RAMIREZ, Rafael, CARRACEDO, Julia, MARTIN-MALO, Alejandro, ALJAMA, Pedro
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antihypertensive agents; Antihypertensive Agents - therapeutic use; Biological and medical sciences; Cardiovascular system; Case-Control Studies; Cell Differentiation - drug effects; Cells, Cultured; Emergency and intensive care: renal failure. Dialysis management; Female; Flow Cytometry; Follow-Up Studies; Humans; Hypertension - immunology; Hypertension - metabolism; Hypertension - prevention & control; Inflammation - immunology; Inflammation - metabolism; Inflammation - prevention & control; Intensive care medicine; Interleukin-10 - metabolism; Interleukin-4 - metabolism; Leukocyte Count; Lipopolysaccharide Receptors - metabolism; Losartan - therapeutic use; Male; Medical sciences; Middle Aged; Monocytes - cytology; Monocytes - drug effects; Monocytes - metabolism; Pharmacology. Drug treatments; Prognosis; Receptors, IgG - metabolism; Renal Dialysis - adverse effects; Renal Insufficiency, Chronic - complications; Renal Insufficiency, Chronic - therapy
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfr767

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 Losartan was withdrawn in five patients from the losartan group for 2 months.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.