Heme oxygenase-1 end-products carbon monoxide and biliverdin ameliorate murine collagen induced arthritis.
OBJECTIVE
Heme oxygenase-1 (HO-1) which degrades Heme to free iron, biliverdin and carbon monoxide (CO) plays an important role in inflammation. There are, however, conflicting data concerning the role of HO-1 in rheumatoid arthritis (RA) and the therapeutic potential of individual heme degradation products remains to be determined. We therefore investigated the effect of CO and biliverdin upon therapeutic administration in the murine collagen induced arthritis (CIA) model of RA.


METHODS
CIA was induced in DBA/1 mice. Anti-CII antibody levels were determined by ELISA. Mice were scored for paw swelling and grip strength. After the first clinical signs of arthritis one group of animals was treated with biliverdin, the second group was treated with CO. After 60 days all animals were sacrificed and analysed for histomorphological signs of arthritis.


RESULTS
All animals immunised with CII developed serum anti-CII antibodies. Antibody levels were decreased in the CO-treated group. Both, Biliverdin and the CO-treated animals, showed an improvement in clinical disease activity. Histological analysis revealed significantly less inflammation, erosion and reduced numbers of osteoclasts in CO-treated animals only, whereas cartilage degradation was prevented in both biliverdin and CO-treated animals.


CONCLUSIONS
Our data demonstrate a beneficial effect of CO, in particular, and biliverdin, on inflammation and bone destruction in the CIA mouse model.
Division of Rheumatology, Internal Medicine III, Medical University of Vienna, Vienna, Austria.
M
M
Bonelli
A
A
Savitskaya
C-W
CW
Steiner
E
E
Rath
M
M
Bilban
O
O
Wagner
F H
FH
Bach
J S
JS
Smolen
C
C
Scheinecker
D000280:Administration, Inhalation; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001664:Biliverdine / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D002248:Carbon Monoxide / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007596:Joints / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice
D002248:Carbon Monoxide; D051547:Heme Oxygenase-1; D001664:Biliverdine