title: Anti-tumor necrosis factor-alpha treatment improves endothelial function in patients with rheumatoid arthritis.
abstract: BACKGROUND
  Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis and increased cardiovascular morbidity and mortality. Striking similarities exist in the inflammatory and immunologic response in RA and atherosclerosis. Indeed, adhesion molecules and cytokines, tumor necrosis factor (TNF)-alpha in particular, are key mediators of joint inflammation and of vascular dysfunction and progression of atherosclerotic vascular disease. Hence, the aim of the present study was to assess the effect of chronic antiinflammatory treatment with the anti-TNF-alpha antibody infliximab on disease activity and endothelial function in patients with active RA.
  
  
  RESULTS
  Eleven RA patients (mean age 46+/-5 years; disease duration 9+/-2 years) with high disease activity despite treatment with stable doses of methotrexate (<or=25 mg/wk) and prednisone (<or=10 mg/d) were investigated. Clinical status and endothelium-dependent and -independent vasodilation of the brachial artery as assessed by high-resolution ultrasound were measured before and after 12 weeks of infliximab therapy. Flow-mediated vasodilation improved from 3.2+/-0.4% to 4.1+/-0.5% (P=0.018), whereas endothelium-independent vasodilation with nitroglycerin and baseline diameter remained unchanged (13.6+/-1.2% versus 12.8+/-1.4%, P=0.98, and 3.74+/-0.15 versus 3.66+/-0.11 mm, P=0.54, respectively). Disease activity score (DAS28) was significantly reduced, from 5.6+/-0.3 to 3.5+/-0.6 (P=0.002). Erythrocyte sedimentation rate and C-reactive protein were lowered from 34+/-7 to 19+/-5 mm/h (P=0.04) and from 38+/-11 to 15+/-10 mg/L (P=0.08), respectively.
  
  
  CONCLUSIONS
  This is the first study to show that anti-TNF-alpha treatment improves endothelial function in RA. The data suggest that in RA, endothelial dysfunction is part of the disease process and is mediated by TNF-alpha.
authors.affiliation: Cardiology Department, University Hospital, Zürich, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Hürlimann
authors.forename: Adrian
authors.initials: A
authors.lastname: Forster
authors.forename: Georg
authors.initials: G
authors.lastname: Noll
authors.forename: Frank
authors.initials: F
authors.lastname: Enseleit
authors.forename: Rémy
authors.initials: R
authors.lastname: Chenevard
authors.forename: Oliver
authors.initials: O
authors.lastname: Distler
authors.forename: Markus
authors.initials: M
authors.lastname: Béchir
authors.forename: Lukas E
authors.initials: LE
authors.lastname: Spieker
authors.forename: Michel
authors.initials: M
authors.lastname: Neidhart
authors.forename: Beat A
authors.initials: BA
authors.lastname: Michel
authors.forename: Renate E
authors.initials: RE
authors.lastname: Gay
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
authors.forename: Steffen
authors.initials: S
authors.lastname: Gay
authors.forename: Frank
authors.initials: F
authors.lastname: Ruschitzka
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology; D002097:C-Reactive Protein / Q000032:analysis; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology; D014463:Ultrasonography; D014664:Vasodilation
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D000069285:Infliximab