Efficacy of daily compared to intermittent administration of IL-1Ra for protection against bone and cartilage destruction in collagen-challenged mice.
OBJECTIVE
To investigate the protective effect of interleukin-1 receptor antagonist (IL-1Ra) on bone and cartilage destruction in the induction phase of collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis (RA).


METHODS
DBA/1J mice were immunized with type II collagen for induction of collagen-induced arthritis (CIA) and simultaneously given different intraperitoneal doses of IL-1Ra daily, thrice weekly or once a week. Clinical symptoms of arthritis were noted daily and assessed using a scoring system during the course of disease. Bone and cartilage destruction in the mice was assessed by radiographic and histological methods respectively.


RESULTS
Mice injected with IL-1Ra daily were completely protected from the occurrence of arthritis after immunization with type II collagen. Moreover, these mice were also protected against bone and cartilage destruction. However, weekly or thrice weekly treatment with IL-1Ra had no effect on arthritis and bone and cartilage destruction.


CONCLUSIONS
Daily administration of recombinant IL-1Ra, injected at the same time as arthritis induction, is effective in blocking the occurrence of inflammatory as well as destructive changes in CIA. Daily bolus injections of IL-1Ra may therefore be useful for protection against joint damage following minor joint injury, whereas the maintenance of appropriate blood levels of the antagonist may be critical for its therapeutic effect on chronic inflammatory arthritis.
Inoue
K
K
Rheumatology, Immunology and Genetics Program, Institute of Medical Science, St. Marianna University of Medicine, Kawasaki, Kanagawa, Japan.
Masuko-Hongo
K
K
Okamoto
M
M
Nishioka
K
K
D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging / Q000473:pathology / Q000517:prevention & control*; D002358:Cartilage, Articular / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006614:Hindlimb; D007274:Injections, Intraperitoneal; D053590:Interleukin 1 Receptor Antagonist Protein; D007596:Joints / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D011859:Radiography; D012720:Severity of Illness Index; D012795:Sialoglycoproteins / Q000008:administration & dosage / Q000627:therapeutic use*
D018501:Antirheumatic Agents; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins