Pharmacologic P2X purinergic receptor antagonism in the treatment of collagen-induced arthritis

OBJECTIVE.: The aim of the present study was to assess the therapeutic potential of a P2X purinergic receptor antagonist, namely periodate oxidized ATP (oATP), in collagen-induced arthritis (CIA). METHODS.: Arthritis was induced in male DBA/1J mice by immunization with type II collagen. Animals showing digits inflammation and paw swelling were treated intraperitoneally each day for 10 days with 100 μl of 3 mM oATP. At the end of treatment animals were sacrificed and paws removed for histological analysis and evaluation of T-cell infiltration. Humoral response to type II collagen was analyzed and specific serum autoantibody levels were correlated to the clinical score observed in the different animal groups. RESULTS: oATP treatment resulted in a sustained reduction of disease activity, which was associated with a significant decrease in CD3+ T-cells infiltration in arthritic lesions and a significant amelioration of cartilage erosion. Peripheral regulatory T cells (Tregs) were significantly increased upon P2X blockade in lymph nodes. Moreover, a marked reduction of circulating autoantibodies directed against mouse collagen type II wasdetected. CONCLUSIONS.: Our findings indicate that P2X receptor antagonism has an important therapeutic potential for chronic inflammatory rheumatic disorders. The therapeutic efficacy was associated with an increase of Tregs in secondary lymphoid organs. Notably, we observed a significant correlation between serum autoantibodies and clinical efficacy exerted by oATP treatment. Together these results underscore the potential value of the P2X receptor signaling pathway as a potential pharmacological target for the modulation of adaptive immunity in CIA.