title: Losartan prevents the development of the pro-inflammatory monocytes CD14+CD16+ in haemodialysis patients.
abstract: 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 Losartan was withdrawn in five patients from the losartan group for 2 months.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 When losartan was withdrawn from five patients in the losartan group, the percentage of CD14+CD16+ monocytes increased compared with before withdrawal.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.
  
  
  CONCLUSIONS
  Losartan acts as an immunomodulator that prevents the development of CD14+CD16+ pro-inflammatory monocytes in HD patients.
authors.affiliation: Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/Fundación de Investigaciones Biomédicas de Córdoba (FIBICO), Córdoba, Spain. merino.a76@gmail.com
authors.forename: Ana
authors.initials: A
authors.lastname: Merino
authors.forename: Maria Antonia
authors.initials: MA
authors.lastname: Alvarez-Lara
authors.forename: Rafael
authors.initials: R
authors.lastname: Ramirez
authors.forename: Julia
authors.initials: J
authors.lastname: Carracedo
authors.forename: Alejandro
authors.initials: A
authors.lastname: Martin-Malo
authors.forename: Pedro
authors.initials: P
authors.lastname: Aljama
mesh_terms: D000959:Antihypertensive Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007958:Leukocyte Count; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011379:Prognosis; D017452:Receptors, IgG / Q000378:metabolism; D006435:Renal Dialysis / Q000009:adverse effects*; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000628:therapy
chemical_list: D000959:Antihypertensive Agents; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D016753:Interleukin-10; D015847:Interleukin-4; D019808:Losartan