title: Immunosuppression and monocyte subsets.
abstract: BACKGROUND
  Monocytes are critical in innate immunity and transplantation. Three monocyte subsets exist, CD14(++)CD16(-), CD14(++)CD16(+) and CD14(+)CD16(++) monocytes; cell counts of CD14(++)CD16(+) and CD14(+)CD16(++) monocytes are increased in pre-transplant chronic kidney disease. Interestingly, the effect of immunosuppressants on monocyte heterogeneity has not been well studied.
  
  
  METHODS
  The impact of immunosuppressants on monocyte subsets was studied: (i) in 152 kidney transplant (KTx) recipients to characterize subset distribution in the steady state, (ii) in patients after autologous (n = 10) versus allogenic (n = 9) haematopoietic stem cell transplantation (HSCT) to analyse monocyte subset development and (iii) in an in vitro model to compare the effect of immunosuppressants on monocyte subset biology.
  
  
  RESULTS
  In KTx, steroid intake was associated with higher total, CD14(++)CD16(-) and CD14(++)CD16(+) monocyte counts, but fewer CD14(+)CD16(++) monocytes, whereas intake of mycophenolate, calcineurin inhibitors (CNI) and mammalian target of rapamycin inhibitors (mTORI) did not affect monocyte (subset) counts. In linear regression analysis, only steroid intake was a significant determinant of monocyte (subset) counts: total monocytes (β = 0.331; P < 0.001), CD14(++)CD16(-) monocytes (β = 0.374; P < 0.001), CD14(++)CD16(+) monocytes (β = 0.221; P = 0.010) and CD14(+)CD16(++) monocytes (β = -0.169; P = 0.049). After HSCT, CD14(++)CD16(-) monocytes were the first to arise, followed by CD14(++)CD16(+) and later by CD14(+)CD16(++) monocytes. Monocyte subset distribution did not differ significantly in patients after allogenic compared with autologous transplantation. CNI, mycophenolate and methotrexate did not influence monocyte subset development, but modified surface receptor expression (CCR2, HLA-DR, ENG, TEK and TLR4) in allogenic HSCT.
  
  
  CONCLUSIONS
  Chronic low-dose steroids are associated with monocytosis and higher counts of CD14(++)CD16(-) and of proinflammatory CD14(++)CD16(+) monocytes.
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany Department of Internal Medicine III, Saarland University Medical Center, Homburg, Germany.
authors.forename: Kyrill S
authors.initials: KS
authors.lastname: Rogacev
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Zawada
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Hundsdorfer
authors.affiliation: Department of Internal Medicine I, Saarland University Medical Center, Homburg, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Achenbach
authors.affiliation: Department of Internal Medicine I, Saarland University Medical Center, Homburg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Held
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany.
authors.forename: Danilo
authors.initials: D
authors.lastname: Fliser
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany.
authors.forename: Gunnar H
authors.initials: GH
authors.lastname: Heine
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000145:classification* / Q000187:drug effects* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D051436:Renal Insufficiency, Chronic / Q000378:metabolism / Q000628:therapy*; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
chemical_list: D015703:Antigens, CD; D007166:Immunosuppressive Agents; D011956:Receptors, Cell Surface
keywords: CD14; CD16; immunosuppression; monocyte; transplantation