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 selecti ve plasma kallikrein inhibitor, PKSI-527, on collagen-induced arthriti s (CIA) in mice. PKSI-527 or indomethacin was administered daily intra peritoneally from day 20 postimmunization. Clinical evaluation was per formed, and two of the components of the kallikrein-kinin system, high -molecular-weight (HMW) kininogen and plasma pre-kallikrein, were assa yed. PKSI-527, as well as indomethacin, reduced the severity of arthri tis significantly. PKSI-527, but not indomethacin, restored consumed c omponents of the kallikrein-kinin system. These results suggest that P KSI-527 suppresses CIA by modifying the kallikrein-kinin system and PK SI-527 as a synthetic plasma kallikrein inhibitor would be a valuable tool to study the mechanism of inflammation of arthritic diseases.