title: CGS 21680, an agonist of the adenosine (A2A) receptor, reduces progression of murine type II collagen-induced arthritis.
abstract: OBJECTIVE
  The aim of our study was to investigate the effect of an adenosine A2A receptor agonist, 2-[p-(2-carboxyethyl)phenylethylamino]-50 ethylcarboxamidoadenosine (CGS 21680), on modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA).
  
  
  METHODS
  CIA was induced by intradermal injection of 100 μl of emulsion containing 100 μg of bovine type II collagen (CII) and complete Freund's adjuvant (CFA) at the base of the tail. On Day 21, a second injection of CII in CFA was administered. Immunized mice developed erosive hind paw arthritis. Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hind paws. The incidence of CIA was 100% by Day 27 in the CII challenged mice and the severity of CIA progressed over a 35-day period, with radiographic evaluation revealing focal resorption of bone. The histopathology of CIA included erosion of cartilage at the joint margins.
  
  
  RESULTS
  Treatment of mice with CGS 21680 starting at the onset of arthritis (Day 25) ameliorated the clinical signs at Days 26-35 and improved histological status in the joint and paw. The degree of oxidative and nitrosative damage was significantly reduced in CGS 21680-treated mice as indicated by elevated levels of malondialdehyde, formation of nitrotyrosine, and activation of poly(ADP-ribose) polymerase. Plasma levels of proinflammatory cytokines such as tumor necrosis factor, interleukin 1ß (IL-1ß) and IL-6 were also reduced by CGS 21680. Treatment with CGS 21680 also decreased the expression of inducible nitric oxide synthase and cyclooxygenase-2.
  
  
  CONCLUSIONS
  We demonstrate that CGS 21680 exerts an antiinflammatory effect during chronic inflammation and ameliorates the tissue damage associated with CIA.
authors.affiliation: Institute of Pharmacology, School of Medicine, University of Messina, Torre Biologica - Policlinico Universitario Via C. Valeria, Gazzi, 98100 Messina, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.forename: Daniela
authors.initials: D
authors.lastname: Impellizzeri
authors.forename: Rosanna
authors.initials: R
authors.lastname: DI Paola
authors.forename: Alessia
authors.initials: A
authors.lastname: Melani
authors.forename: Placido
authors.initials: P
authors.lastname: Bramanti
authors.forename: Felicita
authors.initials: F
authors.lastname: Pedata
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; 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; D024043:Collagen Type II / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D018450:Disease Progression; D015850:Interleukin-6 / Q000378:metabolism; D007596:Joints / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010627:Phenethylamines / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D058908:Adenosine A2 Receptor Agonists; D024043:Collagen Type II; D015850:Interleukin-6; D010627:Phenethylamines; D014409:Tumor Necrosis Factor-alpha; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D000241:Adenosine