title: Differential effects of IL-6 blockade tocilizumab and TNF inhibitors on angiogenesis in synovial tissues from patients with rheumatoid arthritis.
abstract: OBJECTIVE
  To compare the influences of tocilizumab (TCZ) and TNF inhibitors (TNFi) on the angiogenesis in synovial tissues of rheumatoid arthritis (RA).
  
  
  METHODS
  Synovial tissues were obtained during joint operations from 13 RA patients treated with TCZ for at least 4 months with or without previous use of TNFi, from 13 RA patients with TNFi alone and from 10 RA patients with only conventional synthetic DMARDs (csDMARDs). Synovial tissues were evaluated by hematoxylin and eosin stain as well as by immunohistological staining with anti-CD31 in which the microvessel densities (MVD) were quantitated. Synovial histopathology was scored for various components.
  
  
  RESULTS
  The most remarkable change in the synovium with TCZ was reduced angiogenesis as well as degeneration of lining layers irrespective of the previous use of TNFi. Thus, MVD in patients treated with TCZ with or without previous TNFi were significantly decreased compared with those in patients with TNFi alone or with csDMARDs. Moreover, MVD was significantly correlated with lining layer proliferation, but not with synovial stromal proliferation or inflammatory changes.
  
  
  CONCLUSIONS
  These results demonstrated that inhibition of angiogenesis is a unique action of TCZ. Moreover, the data also suggest that lining layers proliferation might be closely associated with angiogenesis.
authors.affiliation: a Department of Rheumatology and Infectious Diseases , Kitasato University School of Medicine , Kanagawa , Japan.
authors.forename: Shunsei
authors.initials: S
authors.lastname: Hirohata
authors.affiliation: b Department of Rheumatology , Niigata Rheumatic Center , Niigata , Japan.
authors.forename: Asami
authors.initials: A
authors.lastname: Abe
authors.affiliation: b Department of Rheumatology , Niigata Rheumatic Center , Niigata , Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Murasawa
authors.affiliation: c Nagano University of Health & Medicine , Nagano , Japan , and.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Kanamono
authors.affiliation: d Department of Orthopedic Surgery , Osaka University Medical School , Osaka , Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tomita
authors.affiliation: d Department of Orthopedic Surgery , Osaka University Medical School , Osaka , Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshikawa
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000473:pathology; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D008297:Male; D008875:Middle Aged; D013583:Synovial Membrane / Q000098:blood supply / Q000473:pathology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D000093242:Interleukin-6 Inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C502936:tocilizumab
keywords: Angiogenesis; Rheumatoid arthritis; Synovium; TNF inhibitors; Tocilizumab