Title

 

Authors

F. Squadrito¹, A. Bitto¹, N. Irrera¹, L. Minutoli¹, M. Rinaldi¹, D. Altavilla¹.

¹Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Italy. 

 

Abstract

The broad anti-inflammatory effects of the adenosine A_2A receptor stimulation  has been demonstrated in acute inflammatory disease, including arthritis. Polydeoxyribonucleotide (PDRN) activates the adenosine A_2A receptor. We investigated the effects of PDRN in collagen-induced arthritis (CIA) in mice. Arthritis was induced in DBA/1 mice by an intra-dermal injection at the base of the tail of 100 µl of emulsion containing bovine type II collagen in complete Freund’s adjuvant. Mice were immunized a second time 21 days later. Control animals received 100 µl of a saline solution. CIA animals were randomized to receive the following treatment: vehicle (1 ml/kg); PDRN (8 mg/kg/ip, daily); 3,7-dimethyl-propargilxanthine (DMPX; 0.1 mg/kg/ip, daily), a specific adenosine A_2A receptor antagonist; PDRN plus DMPX. The treatment was initiated immediately after the second immunization and lasted up to day 45. Clinical evaluation of arthritis was evaluated throughout the study. At day 45 the animals were euthanized to evaluate the severity of arthritis histologically and to investigate the cartilage expression and the circulating levels of High  Mobility Group  box -1 (HMGB-1), Tumor Necrosis Factor-α  (TNF-α ), Interleukin-6 (IL-6) and Interleukin-10 (IL-10). PDRN treatment significantly ameliorated the clinical signs of arthritis and the arthritis index, improved the histological  damage, reduced the cartilage expression and the circulating levels of HMGB-1, TNF-α , IL-6 and enhanced IL-10 expression. The concomitant administration of DMPX  a specific adenosine A_2A receptor antagonist abated the PDRN induced protective effect in experimental arthritis. PDRN may, therefore, represents a new therapeutic alternative for the treatment of  arthritis.