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

Iain B McInnes1, Simon Cruwys, Keith Bowers

  • 1Glasgow Biomedical Research Centre, University of Glasgow, UK. iain.mcinnes@glasgow.ac.uk.

Clinical and Experimental Rheumatology
|October 8, 2014
PubMed
Abstract

Insights

Inhibiting the P2X7 receptor reduced inflammation and joint damage in rat models of rheumatoid arthritis. This suggests P2X7 receptor blockers may offer a new treatment for inflammatory arthritis.

Area of Science:

  • Immunology
  • Rheumatology
  • Pharmacology

Background:

  • Rheumatoid arthritis (RA) is a chronic inflammatory disease.
  • The P2X7 receptor (P2X7R) is implicated in inflammatory processes.

Purpose of the Study:

  • To investigate the role of the P2X7 receptor in preclinical models of rheumatoid arthritis.
  • To evaluate the efficacy of a novel P2X7R inhibitor, AZD9056, in reducing inflammatory markers.

Main Methods:

  • Utilized the rat streptococcal cell wall (SCW)-induced arthritis model.
  • Assessed P2X7R expression in inflamed synovial tissue.
  • Tested AZD9056 in ex vivo human monocyte cultures stimulated with lipopolysaccharide (LPS) and benzoylbenzoyl adenosine triphosphate (BzATP).

Main Results:

  • P2X7 receptor was expressed in inflamed joints of arthritic rats.
  • P2X7R inhibition significantly reduced joint inflammation and erosive progression.
  • AZD9056 inhibited the release of interleukin (IL)-1 and IL-18 from stimulated human monocytes.

Conclusions:

  • P2X7 receptor inhibition demonstrates therapeutic potential for inflammatory arthritis.
  • Further clinical studies are necessary to confirm the efficacy of P2X7R inhibition in human patients.

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