Targeting the P2X7 receptor in rheumatoid arthritis: biological rationale for P2X7 antagonism

摘要: Objectives: This paper aims to explore the functional significance of P2X7 receptor in preclinical models rheumatoid arthritis. Methods: Preclinical studies vivo were performed using rat streptococcal cell wall (SCW) arthritis model. Ex cultures lipopolysaccharide (LPS)/benzoylbenzoyl adenosine triphosphate (BzATP)-stimulated human monocytes generated test activities a novel, highly specific inhibitor P2X7, AZD9056, on interleukin (IL)-1 and IL-18 release. Results: P2X7 expression was detected inflamed synovial tissue after onset SCW-induced rats. Inhibition therein led reduced articular inflammation erosive progression. No effect noted acute-phase responses. vivo, AZD9056 inhibited IL-1 release BzATP LPS-primed monocytes. Conclusions: P2X7 inhibition could represent novel approach treatment inflammatory arthritis. However, confirmatory clinical are warranted further this possibility.