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.