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.

CONCLUSION:

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: Vittoria Ardissone, Enrico Radaelli, Paola Zaratin, Michele Ardizzone, Christoph Ladel, Marco Gattorno, Alberto Martini, Fabio Grassi, Elisabetta Traggiai
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 63 Issue 11 Pg. 3323-32 (Nov 2011) ISSN: 1529-0131 [Electronic] United States
• PMID: 21792831 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 by the American College of Rheumatology.

Chemical References

• Autoantibodies
• Collagen Type II
• Purinergic P2X Receptor Antagonists
• 2',3'-dialdehyde ATP
• Adenosine Triphosphate

Topics

• Adenosine Triphosphate (analogs & derivatives, pharmacology, therapeutic use)
• Animals
• Arthritis, Experimental (chemically induced, drug therapy, immunology)
• Autoantibodies (immunology)
• Collagen Type II (administration & dosage)
• Lymph Nodes (drug effects)
• Male
• Mice
• Purinergic P2X Receptor Antagonists (pharmacology, therapeutic use)
• T-Lymphocytes, Regulatory (drug effects, immunology)