title: Pharmacologic P2X purinergic receptor antagonism in the treatment of collagen-induced arthritis.
abstract: OBJECTIVE
  To assess the therapeutic potential of a P2X purinergic receptor antagonist, namely, periodate oxidized ATP, in collagen-induced arthritis (CIA).
  
  
  METHODS
  Arthritis was induced in male DBA/1J mice by immunization with type II collagen (CII). Animals showing digit inflammation and paw swelling were treated intraperitoneally with 100 μl of 3 mM oxidized ATP daily for 10 days. At the end of the treatment period, animals were killed and paws were removed for histologic analysis and evaluation of T cell infiltration. Humoral response to CII was analyzed, and specific serum autoantibody levels were correlated with the clinical scores observed in the different treatment groups.
  
  
  RESULTS
  Treatment with oxidized ATP resulted in a sustained reduction in disease activity, which was associated with a significant decrease in CD3+ T cell infiltration in arthritic lesions and a significant amelioration of cartilage erosion. Peripheral Treg cells were significantly increased upon P2X blockade in mouse lymph nodes. Moreover, a marked reduction in circulating autoantibodies directed against mouse CII was detected. There was a significant correlation between serum autoantibody levels and the clinical efficacy of oxidized ATP.
  
  
  CONCLUSIONS
  Our findings indicate that P2X receptor antagonism has important therapeutic potential in chronic inflammatory rheumatic disorders. Taken together, our results underscore the value of the P2X receptor signaling pathway as a potential pharmacologic target for the modulation of adaptive immunity in CIA.
authors.affiliation: Merck Serono SA RBM SpA Istituto di Ricerche Biomediche Antoine Marxer, Turin, Italy. vittoria.ardissone@procelltech.net
authors.forename: Vittoria
authors.initials: V
authors.lastname: Ardissone
authors.forename: Enrico
authors.initials: E
authors.lastname: Radaelli
authors.forename: Paola
authors.initials: P
authors.lastname: Zaratin
authors.forename: Michele
authors.initials: M
authors.lastname: Ardizzone
authors.forename: Christoph
authors.initials: C
authors.lastname: Ladel
authors.forename: Marco
authors.initials: M
authors.lastname: Gattorno
authors.forename: Alberto
authors.initials: A
authors.lastname: Martini
authors.forename: Fabio
authors.initials: F
authors.lastname: Grassi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Traggiai
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D024043:Collagen Type II / Q000008:administration & dosage; D008198:Lymph Nodes / Q000187:drug effects; D008297:Male; D051379:Mice; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology
chemical_list: D001323:Autoantibodies; D024043:Collagen Type II; D058920:Purinergic P2X Receptor Antagonists; C017199:2',3'-dialdehyde ATP; D000255:Adenosine Triphosphate