title: Tocilizumab treatment decreases circulating myeloid dendritic cells and monocytes, 2 components of the myeloid lineage.
abstract: OBJECTIVE
  Interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) are proinflammatory cytokines involved in inflammatory response. Effective TNF-α blocker treatment is associated with an increase in circulating myeloid dendritic cells (mDC), suggesting their release from inflamed synovium. Currently, in vivo effects of IL-6 inhibition on DC are unknown. We monitored the changes in circulating mDC and plasmacytoid DC (pDC) during tocilizumab (TCZ) therapy in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  DC subset levels were evaluated by flow cytometry in patients with RA (n = 43) and in healthy volunteers (n = 20). In patients with RA, these levels were measured before and during TCZ therapy (8 mg/kg every 4 weeks). Response to TCZ therapy was evaluated at 12 weeks. Statistical analysis was based on Mann-Whitney U tests or Wilcoxon signed-rank tests.
  
  
  RESULTS
  At baseline, patients with active RA were characterized by a significantly lower level of circulating mDC and pDC compared to healthy donors. However, this difference did not correlate with any disease activity score. TCZ-treated patients who met the European League Against Rheumatism (EULAR) improvement criteria at Week 12 had significant reductions in mDC and monocyte levels as compared with EULAR nonresponders. Levels of pDC, CD4+ T cells, and CD8+ T cells remained stable during the TCZ courses, regardless of treatment response.
  
  
  CONCLUSIONS
  Our study reveals an unexpected reduction of circulating mDC and monocytes in patients with RA in response to TCZ therapy. In accord with reports on neutrophils and platelets decreasing during TCZ therapy, our data suggest an effect of IL-6 inhibition on cells from myeloid lineage.
authors.affiliation: Département de Rhumatologie, CHU Bordeaux, Hôpital Pellegrin, Place Amélie Raba Léon, 33076 Bordeaux, France. christophe.richez@chu-bordeaux.fr
authors.forename: Christophe
authors.initials: C
authors.lastname: Richez
authors.forename: Thomas
authors.initials: T
authors.lastname: Barnetche
authors.forename: Liliane
authors.initials: L
authors.lastname: Khoryati
authors.forename: Pierre
authors.initials: P
authors.lastname: Duffau
authors.forename: Marie
authors.initials: M
authors.lastname: Kostine
authors.forename: Cécile
authors.initials: C
authors.lastname: Contin-Bordes
authors.forename: Patrick
authors.initials: P
authors.lastname: Blanco
authors.forename: Thierry
authors.initials: T
authors.lastname: Schaeverbeke
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D018501:Antirheumatic Agents / Q000494:pharmacology*; D018771:Arthralgia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000473:pathology; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D006304:Health Status; D006801:Humans; D007596:Joints / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000473:pathology; D017063:Outcome Assessment, Health Care; D010147:Pain Measurement; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C502936:tocilizumab