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Treatment with a CO-releasing molecule (CORM-3) reduces joint inflammation and erosion in murine collagen-induced arthritis
  1. M L Ferrándiz1,
  2. N Maicas1,
  3. I Garcia-Arnandis1,
  4. M C Terencio1,
  5. R Motterlini2,
  6. I Devesa3,
  7. L A B Joosten3,
  8. W B van den Berg3,
  9. M J Alcaraz1
  1. 1
    Department of Pharmacology, University of Valencia, Valencia, Spain
  2. 2
    Vascular Biology Unit, Department of Surgical Research, Northwick Park Institute for Medical Research, Harrow, Middlesex, UK
  3. 3
    Rheumatology Research & Advanced Therapeutics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  1. Professor M J Alcaraz, Department of Pharmacology, University of Valencia, Avda. Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain; maria.j.alcaraz{at}


Objective: CO-releasing molecules (CO-RMs) are a novel class of anti-inflammatory agents. We have examined the possible therapeutic effects of CORM-3 in collagen-induced arthritis (CIA).

Methods: Arthritis was induced in DBA-1/J mice by type II collagen. Animals were treated with CORM-3 (5 and 10 mg/kg/day, intraperitoneally) or the inactive compound iCORM-3 (10 mg/kg/day, intraperitoneally) unable to release CO, from days 22 to 31. Production of anti-type II collagen antibodies, cytokines and cartilage olimeric matrix protein (COMP) was evaluated by enzyme-linked immunosorbent assay, and prostaglandin E2 (PGE2) by radioimmunoassay. Localisation of cyclooxygenase-2 (COX-2), haem oxygenase-1 (HO-1), intercellular adhesion molecule-1 (ICAM-1) and receptor activator of nuclear factor κB ligand (RANKL) was examined by immunohistochemistry.

Results: Therapeutic administration of CORM-3 suppressed clinical and histopathological manifestations of disease. The levels of PGE2, interleukin (IL)1β, IL2, IL6, IL10 and tumour necrosis factor (TNF)α in joint tissues were inhibited by CORM-3. By contrast, CORM-3 augmented IL4. Anti-type II collagen antibodies and COMP levels in serum were reduced by CORM-3. Treatment with CORM-3 decreased cellular infiltration, joint inflammation and destruction, as well as the expression of COX-2, ICAM-1 and RANKL, whereas HO-1 increased. These beneficial effects were due to CO release, as iCORM-3 was ineffective.

Conclusion: This study reveals the antiarthritic properties of CORM-3 in the CIA model and supports the notion that CO-RMs could be developed as a novel strategy for the treatment of inflammatory and arthritic conditions.

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  • Funding: This work was funded by public grants from Spanish Ministerio de Educación y Ciencia-FEDER (SAF2004-03835 and N Maicas fellowship) and Generalitat Valenciana (ACOMP2007-066, GV06/357 and I Garcia-Arnandis fellowship).

  • Competing interests: RM has financial interests in Hemocorm.