title: Neutrophil respiratory burst is decreased in scleroderma and normalized by near-infrared mediated hyperthermia.
abstract: BACKGROUND
  The production of reactive oxygen species (ROS) by fibroblasts has been suggested to contribute to scleroderma pathogenesis. Infrared-mediated hyperthermia has recently been shown to be of benefit in scleroderma.
  
  
  OBJECTIVE
  As the contribution of neutrophils and monocytes to ROS formation in scleroderma is unknown, we studied respiratory burst in these cell types. We also aimed to test the hypothesis that near-infrared (IRA) treatment may effect burst activity.
  
  
  METHODS
  We determined respiratory burst in patients with scleroderma (n = 22) and age- and sex-matched controls (n = 20) at baseline, and after high-level stimulation by phorbolmyristyl acetate (PMA) and low-level stimulation by non-opsonized zymosan. Respiratory burst was also assessed before and after a series of infrared-mediated hyperthermia treatments.
  
  
  RESULTS
  Unexpectedly, we observed no increase but instead a slight but statistically significant reduction in baseline and zymosan-stimulated respiratory burst in scleroderma neutrophils (P < 0.001) and monocytes (P < 0.005). This decrease in burst activity was nonspecific, as it was also observed in patients with another active inflammatory disease, psoriasis. IRA treatment induced a cell-type-specific normalization of respiratory burst only in neutrophils, but not in monocytes. Intriguingly, neutrophil-specific normalization of ROS formation persisted for 6 weeks after the end of IRA treatment, in concordance with the previously reported clinical responses to this therapy.
  
  
  CONCLUSIONS
  Neutrophils and monocytes do not exhibit cell-autonomous overproduction of ROS in scleroderma, thereby implicating fibroblasts as main source for clinically relevant ROS accumulation. Furthermore, repeated mild infrared-mediated hyperthermia exerts a lasting cell-type-specific effect on neutrophils.
authors.affiliation: Department of Dermatology, Charité Hospital, Berlin, Germany. john.foerster@charite.de
authors.forename: J
authors.initials: J
authors.lastname: Foerster
authors.forename: A
authors.initials: A
authors.lastname: Storch
authors.forename: S
authors.initials: S
authors.lastname: Fleischanderl
authors.forename: S
authors.initials: S
authors.lastname: Wittstock
authors.forename: S
authors.initials: S
authors.lastname: Pfeiffer
authors.forename: G
authors.initials: G
authors.lastname: Riemekasten
authors.forename: M
authors.initials: M
authors.lastname: Worm
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D007259:Infrared Rays / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000097:blood; D016897:Respiratory Burst / Q000187:drug effects; D012595:Scleroderma, Systemic / Q000097:blood* / Q000628:therapy; D012720:Severity of Illness Index; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D046509:Tissue Culture Techniques; D015054:Zymosan / Q000494:pharmacology
chemical_list: D017382:Reactive Oxygen Species; D015054:Zymosan; D013755:Tetradecanoylphorbol Acetate