title: Oral treatment with complement factor C5a receptor (CD88) antagonists inhibits experimental periodontitis in rats.
abstract: OBJECTIVE
  The complement activation product 5a (C5a) is a potent mediator of the innate immune response to infection, and may thus also importantly determine the development of periodontitis. The present study was designed to explore the effect of several novel, potent and orally active C5a receptor (CD88) antagonists (C5aRAs) on the development of ligature-induced periodontitis in an animal model.
  
  
  METHODS
  Three different cyclic peptide C5aRAs, termed PMX205, PMX218 and PMX273, were investigated. Four groups of Wistar rats (n = 10 in each group) were used. Starting 3 d before induction of experimental periodontitis, rats either received one of the C5aRas (1-2 mg/kg) in the drinking water or received drinking water only. Periodontitis was assessed when the ligatures had been in place for 14 d.
  
  
  RESULTS
  Compared with control rats, PMX205- and PMX218-treated rats had significantly reduced periodontal bone loss.
  
  
  CONCLUSIONS
  The findings suggest that complement activation, and particularly C5a generation, may play a significant role in the development and progression of periodontitis. Blockade of the major C5a receptor, CD88, with specific inhibitors such as PMX205, may offer novel treatment options for periodontitis.
authors: Department of Periodontology, Faculty of Dentistry, University of Oslo, Oslo, Norway. tbreivik@odont.uio.no
authors: T
authors: T
authors: Breivik
authors: Y
authors: Y
authors: Gundersen
authors: P
authors: P
authors: Gjermo
authors: S M
authors: SM
authors: Taylor
authors: T M
authors: TM
authors: Woodruff
authors: P K
authors: PK
authors: Opstad
mesh_terms: D016301:Alveolar Bone Loss / Q000276:immunology / Q000517:prevention & control*; D000818:Animals; D003167:Complement Activation; D004195:Disease Models, Animal; D060766:Drinking Water; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D007167:Immunotherapy / Q000379:methods; D008026:Ligation; D010456:Peptides, Cyclic / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D010518:Periodontitis / Q000276:immunology / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D044087:Receptor, Anaphylatoxin C5a / Q000037:antagonists & inhibitors*
chemical_list: D060766:Drinking Water; D007155:Immunologic Factors; D010456:Peptides, Cyclic; D044087:Receptor, Anaphylatoxin C5a; C570577:hydrocinnamate-(OP(Phe)WR); C570578:hydrocinnamate-AcF-(OP(Phe)WR); C504156:hydrocinnamate-cyclo(ornithyl-prolyl-cyclohexylalanyl-tryptophyl-arginyl)