Effects of a highly selective plasma kallikrein inhibitor on collagen-induced arthritis in mice.
A study was conducted to evaluate the effects of a new, highly selective plasma kallikrein inhibitor, PKSI-527, on collagen-induced arthritis (CIA) in mice. PKSI-527 or indomethacin was administered daily intraperitoneally from day 20 postimmunization. Clinical evaluation was performed, and two of the components of the kallikrein-kinin system, high-molecular-weight (HMW) kininogen and plasma prekallikrein, were assayed. PKSI-527, as well as indomethacin, reduced the severity of arthritis significantly. PKSI-527, but not indomethacin, restored consumed components of the kallikrein-kinin system. These results suggest that PKSI-527 suppresses CIA by modifying the kallikrein-kinin system and PKSI-527 as a synthetic plasma kallikrein inhibitor would be a valuable tool to study the mechanism of inflammation of arthritic diseases.
Fujimori
Y
Y
Department of Orthopaedic Surgery, Faculty of Medicine, Kyoto University, Japan.
Nakamura
T
T
Shimizu
K
K
Yamamuro
T
T
Wanaka
K
K
Okamoto
S
S
Katsuura
Y
Y
D000818:Animals; D001169:Arthritis, Experimental / Q000473:pathology / Q000517:prevention & control*; D003094:Collagen; D007213:Indomethacin / Q000627:therapeutic use; D007610:Kallikreins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007704:Kininogens / Q000097:blood; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011288:Prekallikrein / Q000378:metabolism; D014148:Tranexamic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
D007704:Kininogens; C064866:PKSI 527; D010649:Phenylalanine; D014148:Tranexamic Acid; D003094:Collagen; D011288:Prekallikrein; D007610:Kallikreins; D007213:Indomethacin