title: Polydeoxyribonucleotide reduces cytokine production and the severity of collagen-induced arthritis by stimulation of adenosine A(₂A) receptor.
abstract: OBJECTIVE
  Broad antiinflammatory effects following adenosine A(₂A) receptor stimulation have been demonstrated in acute inflammatory diseases, including arthritis. Polydeoxyribonucleotide (PDRN) activates the adenosine A(₂A) receptor. This study was undertaken to investigate the effects of PDRN in collagen-induced arthritis (CIA) in mice.
  
  
  METHODS
  Arthritis was induced in DBA/1 mice by an intradermal injection of 100 μl of bovine type II collagen in Freund's complete adjuvant. Mice were immunized a second time 21 days later. Control animals received 100 μl of a saline solution. Animals with CIA were randomized to receive one of the following: vehicle (1 ml/kg); PDRN (8 mg/kg intraperitoneally daily); 3,7-dimethyl-propargylxanthine (DMPX), a specific adenosine A(₂A) receptor antagonist (0.1 mg/kg intraperitoneally daily); or PDRN plus DMPX. The treatment was initiated immediately after the second immunization and continued to day 45. Clinical evaluation of arthritis was performed throughout the study. On day 45, the animals were killed and the severity of arthritis was evaluated histologically. Cartilage expression and circulating levels of high mobility group box chromosomal protein 1 (HMGB-1), tumor necrosis factor α (TNFα), interleukin-6 (IL-6), and IL-10 were investigated. Inflammatory cytokine production was also evaluated in stimulated human chondrocytes treated with PDRN.
  
  
  RESULTS
  PDRN treatment significantly ameliorated clinical signs of arthritis, improved histologic damage, reduced the cartilage expression and circulating levels of HMGB-1, TNFα, and IL-6, and enhanced IL-10 expression. The concomitant administration of DMPX and PDRN ablated the PDRN-induced protective effect in experimental arthritis. PDRN also reduced cytokine production from stimulated human chondrocytes.
  
  
  CONCLUSIONS
  Our findings indicate that PDRN may represent a new alternative for the treatment of arthritis.
authors.affiliation: University of Messina, Messina, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bitto
authors.forename: Francesca
authors.initials: F
authors.lastname: Polito
authors.forename: Natasha
authors.initials: N
authors.lastname: Irrera
authors.forename: Angela
authors.initials: A
authors.lastname: D'Ascola
authors.forename: Angela
authors.initials: A
authors.lastname: Avenoso
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Nastasi
authors.forename: Giuseppe M
authors.initials: GM
authors.lastname: Campo
authors.forename: Antonio
authors.initials: A
authors.lastname: Micali
authors.forename: Gianfilippo
authors.initials: G
authors.lastname: Bagnato
authors.forename: Letteria
authors.initials: L
authors.lastname: Minutoli
authors.forename: Herbert
authors.initials: H
authors.lastname: Marini
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Rinaldi
authors.forename: Francesco
authors.initials: F
authors.lastname: Squadrito
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
mesh_terms: D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D024043:Collagen Type II / Q000008:administration & dosage; D024243:HMGB1 Protein / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D011089:Polydeoxyribonucleotides / Q000494:pharmacology / Q000627:therapeutic use*; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D058908:Adenosine A2 Receptor Agonists; D024043:Collagen Type II; D024243:HMGB1 Protein; D015850:Interleukin-6; D011089:Polydeoxyribonucleotides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10