Effect of human plasma-type platelet-activating factor acetylhydrolase in two anaphylactic shock models

The effect of human recombinant plasma-type platelet-activating factor (PAF) acetylhydrolase was examined in two murine models, PAF-induced death and active anaphylactic models. In the PAF-induced death model where mice were injected intravenously with 40 mu g/kg of PAF, the administration of PAF acetylhydrolase reduced mortality in a dose-dependent manner, showing complete prevention of mortality at 1.0 mg/kg. Myeloperoxidase activity, the marker for neutrophils, was increased in the lung by PAF injection, and the PAF acetylhydrolase treatment significantly reversed the increase in myeloperoxidase activity. As in the PAF-induced model, PAF acetylhydrolase also decreased mortality in the active anaphylactic shock model where bovine serum albumin was injected intravenously to mice previously immunized with bovine serum albumin. The protective effect of PAF acetylhydrolase on mortality in this model was significant at 1.0 mg/kg. These results suggest that PAF is an important mediator in the lethality of systemic anaphylaxis, and that PAF acetylhydrolase may be beneficial for treatment of anaphylactic shock (C) 2000 Elsevier Science B.V. All rights reserved.