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

BACKGROUND: 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. METHODS: 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 Losartan was withdrawn in five patients from the losartan group for 2 months.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. RESULTS: 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 When losartan was withdrawn from five patients in the losartan group, the percentage of CD14+CD16+ monocytes increased compared with before withdrawal.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. CONCLUSION: Losartan acts as an immunomodulator that prevents the development of CD14+CD16+ pro-inflammatory monocytes in HD patients.