title: Early inflammatory changes in radiation-induced oral mucositis : Effect of pentoxifylline in a mouse model.
abstract: OBJECTIVE
  Early inflammation is a major factor of mucosal reactions to radiotherapy. Pentoxifylline administration resulted in a significant amelioration of radiation-induced oral mucositis in the mouse tongue model. The underlying mechanisms may be related to the immunomodulatory properties of the drug. The present study hence focuses on the manifestation of early inflammatory changes in mouse tongue during daily fractionated irradiation and their potential modulation by pentoxifylline.
  
  
  METHODS
  Daily fractionated irradiation with 5 fractions of 3 Gy/week (days 0-4, 7-11) was given to the snouts of mice. Groups of 3 animals per day were euthanized every second day between day 0 and 14. Pentoxifylline (15 mg/kg, s. c.) was administered daily from day 5 to the day before sacrifice. The expression of the inflammatory proteins TNFα, NF-κB, and IL-1β were analysed.
  
  
  RESULTS
  Fractionated irradiation increased the expression of all inflammatory markers. Pentoxifylline significantly reduced the expression of TNFα and IL-1β, but not NF-κB.
  
  
  CONCLUSIONS
  Early inflammation, as indicated by the expression of the inflammatory markers TNFα, NF-κB, and IL-1β, is an essential component of early radiogenic oral mucositis. Pentoxifylline differentially modulated the expression of different inflammatory markers. The mucoprotective effect of pentoxifylline does not appear to be based on modulation of NF-κB-associated inflammation.
authors.affiliation: Applied and Translational Radiobiology, Dept. Radiation Oncology/CD Lab. Med. Radiation Research for Radiation Oncology, Medical University/AKH Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. sylvia.gruber@meduniwien.ac.at.
authors.forename: Sylvia
authors.identifier: http://orcid.org/0000-0001-5280-1676
authors.initials: S
authors.lastname: Gruber
authors.affiliation: Applied and Translational Radiobiology, Dept. Radiation Oncology/CD Lab. Med. Radiation Research for Radiation Oncology, Medical University/AKH Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors.forename: Eva
authors.initials: E
authors.lastname: Bozsaky
authors.affiliation: Applied and Translational Radiobiology, Dept. Radiation Oncology/CD Lab. Med. Radiation Research for Radiation Oncology, Medical University/AKH Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors.forename: Eva
authors.initials: E
authors.lastname: Roitinger
authors.affiliation: Applied and Translational Radiobiology, Dept. Radiation Oncology/CD Lab. Med. Radiation Research for Radiation Oncology, Medical University/AKH Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors.forename: Karoline
authors.initials: K
authors.lastname: Schwarz
authors.affiliation: Dept. Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.|OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Fetscherstr. 74, 01307, Dresden, Germany.
authors.forename: Margret
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Applied and Translational Radiobiology, Dept. Radiation Oncology/CD Lab. Med. Radiation Research for Radiation Oncology, Medical University/AKH Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.|Dept. Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.|OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Fetscherstr. 74, 01307, Dresden, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dörr
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019583:Dose Fractionation, Radiation; D018836:Inflammation Mediators / Q000032:analysis; D051379:Mice; D008809:Mice, Inbred C3H; D009061:Mouth Mucosa / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects*; D010431:Pentoxifylline / Q000494:pharmacology*; D011832:Radiation Injuries / Q000188:drug therapy* / Q000473:pathology*; D013280:Stomatitis / Q000188:drug therapy* / Q000473:pathology*; D014059:Tongue / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects
chemical_list: D018836:Inflammation Mediators; D010431:Pentoxifylline
keywords: Animal model; Fractionated irradiation; Head and neck cancer; Oral mucositis; Radiation protection