, Volume 32, Issue 2, pp 83–88 | Cite as

Inhalation of Carbon Monoxide Ameliorates Collagen-induced Arthritis in Mice and Regulates the Articular Expression of IL-1β and MCP-1

  • Tomohisa Takagi
  • Yuji Naito
  • Mamoru Inoue
  • Satomi Akagiri
  • Katsura Mizushima
  • Osamu Handa
  • Satoshi Kokura
  • Hiroshi Ichikawa
  • Toshikazu Yoshikawa


Carbon monoxide (CO), long considered a toxic gas, has recently been shown to mediate anti-inflammatory effects in various animal models. The aim of this study was to investigate whether the inhalation of CO ameliorated collagen-induced arthritis (CIA) in mice. CIA was induced in female DBA/1 mice by the injection of an anti-type II collagen antibody and lipopolysaccharide. The CO treatment group was exposed to CO gas at a concentration of 200 ppm in a closed cage starting on the day of the injection with an anti-type II collagen antibody and throughout the remaining study period. The clinical arthritis scores was examined daily for swelling of the paws as a sign of arthritis. For histopathology, the sections of the hind legs were evaluated by hematoxylin-eosin staining. Moreover, we evaluated the expression of interleukin (IL)-1β and monocyte chemoattractant protein-1 (MCP-1) mRNA in the hind paws. Both clinical arthritis scores as well as histological findings of joint inflammation were significantly reduced in mice treated with CO gas inhalation compared to untreated mice. Further, CO significantly inhibited the increased expression of IL-1β and MCP-1 mRNA in paws at day 3 after the induction of arthritis. In conclusion, the inhalation of CO protected mice from the synovial inflammation of CIA. Based on these data, the beneficial effects of CO in murine RA model may be attributed to its anti-inflammatory properties.


carbon monoxide collagen-induced arthritis heme oxygenase 



This work was supported by a Grant-in-Aid for scientific research (Grant no. 18590694) from the Ministry of Health, Labour and Welfare of Japan.


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Tomohisa Takagi
    • 1
  • Yuji Naito
    • 1
  • Mamoru Inoue
    • 2
  • Satomi Akagiri
    • 3
  • Katsura Mizushima
    • 1
  • Osamu Handa
    • 1
  • Satoshi Kokura
    • 1
  • Hiroshi Ichikawa
    • 1
  • Toshikazu Yoshikawa
    • 1
    • 3
  1. 1.Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical SienceKyoto Prefectural University of MedicineKyotoJapan
  2. 2.Department of Internal MedicineKyoto Second Red Cross HospitalKyotoJapan
  3. 3.Biomedical Safety Science, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan

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