The effect of endostatin evaluated in an experimental animal model of collagen-induced arthritis.
OBJECTIVE
To investigate the arthritis-inhibiting effect of endostatin, a potent angiogenesis inhibitor, on type II collagen-induced arthritis (CIA).


METHODS
In an experimental system of prophylactic administration, endostatin was administered once daily at 1 mg/kg/day or 10 mg/kg/day for 2 weeks from before the onset of arthritis. In the experimental system of therapeutic administration, mice with an arthritis score of 1 to 3 were administered endostatin once daily at 10 mg/kg. In the experimental system of continuous administration, endostatin was administered using an osmotic pump capable of continuously administering a calculated dose of 1 mg/kg/day for 2 weeks.


RESULTS
Arthritis scores were lower in a dose-dependent manner in the prophylactic administration group than in the control group. Arthritis scores were lower in the therapeutic administration group than in the control group. Compared with the once-daily dosage regimen, the administration of endostatin by an osmotic pump achieved a similar arthritis-inhibiting effect at one-tenth of the dose.


CONCLUSIONS
Both prophylactic and therapeutic administration of endostatin inhibited type II CIA in mice. The administration method using an osmotic pump is useful.
Kurosaka
D
D
Division of Rheumatology, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan. d_kurosaka@jikei.ac.jp
Yoshida
K
K
Yasuda
J
J
Yasuda
C
C
Noda
K
K
Furuya
K
K
Ukichi
T
T
Kingetsu
I
I
Joh
K
K
Yamaguchi
N
N
Saito
S
S
Yamada
A
A
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D024043:Collagen Type II / Q000633:toxicity; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D043169:Endostatins / Q000008:administration & dosage*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D015870:Gene Expression; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D012313:RNA / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D015415:Biomarkers; D024043:Collagen Type II; D016207:Cytokines; D043169:Endostatins; D012313:RNA