title: Neutrophil migration and production of reactive oxygen species during treatment with a fully human anti-tumor necrosis factor-alpha monoclonal antibody in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  To evaluate the effects of therapy with a fully human anti-tumor necrosis factor (TNF)-alpha monoclonal antibody on the production of superoxide and other reactive oxygen species (ROS) and on the migration capacity of neutrophils in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  A total of 29 patients with active RA and 25 healthy controls participated. Assessments were performed at baseline and 2 weeks after the first administration of anti-TNF-alpha. The production of ROS was studied in unstimulated conditions and after stimulation of receptor dependent (serum treated zymosan, STZ) and receptor independent (phorbol mystrate acetate, PMA) pathways by luminol enhanced chemiluminescence. As well, the PMA induced burst production of superoxide was measured using the cytochrome-c reduction assay. Potential changes in neutrophil migration to joints were assessed by scintigraphy with autologous leukocytes.
  
  
  RESULTS
  Baseline production of ROS (both spontaneously and after STZ stimulation) and superoxide and the ex vivo chemotaxis were similar in RA patients (n = 25) and controls (n = 25) and remained unchanged after administration of anti-TNF-alpha. The production of ROS after PMA stimulation was slightly higher in patients than in controls (p = 0.04) and this difference disappeared 2 weeks after the first dose of anti-TNF-alpha (p < 0.05). The scintigraphic study showed that a single dose of anti-TNF-alpha, but not placebo, markedly decreased the influx of leukocytes to inflamed joints.
  
  
  CONCLUSIONS
  In patients with RA, anti-TNF-alpha therapy rapidly decreases the influx of leukocytes into inflamed joints but does not impair neutrophil chemotaxis and production of ROS.
authors.affiliation: Department of Rheumatology, University Medical Center Nijmegen, Nijmegen, The Netherlands. A.denbroeder@aig.azn.nl
authors.forename: Alfons A
authors.initials: AA
authors.lastname: den Broeder
authors.forename: Geert J A
authors.initials: GJ
authors.lastname: Wanten
authors.forename: Wim J G
authors.initials: WJ
authors.lastname: Oyen
authors.forename: Ton
authors.initials: T
authors.lastname: Naber
authors.forename: Piet L C M
authors.initials: PL
authors.lastname: van Riel
authors.forename: Pilar
authors.initials: P
authors.lastname: Barrera
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000276:immunology / Q000628:therapy*; D002465:Cell Movement / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D011877:Radionuclide Imaging; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016897:Respiratory Burst / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab