BACKGROUND: This study was to clarify the effects of gabexate mesilate (Foy^®), a synthetic protease inhibitor, on endotoxin induced acute lung injury in rabbit.

METHODS: Animals were randomly assigned to one of four groups: saline only (n = 7), saline and Escherichia coli endotoxin 5 mg/kg over 30 mins (n = 7), Foy^® 1 mg/kg bolus, followed by infusion of Foy^® at 1 mg/kg/h and endotoxin (n = 7), Foy^® 2 mg/kg bolus, followed by infusion of Foy^® at 2 mg/kg/h and endotoxin (n = 7). Infusion of saline or Foy^® was started 0.5 hour before the start of infusion of saline or endotoxin and continued for 6.5 hours. At the end infusion animals were sacrificed, and the wet to dry (W/D) weight ratio of lung, lung injury score and leukocyte counts, percentage of polymorphonuclear leukocyte (PMNL), and concentrations of albumin and interleukin-8 (IL-8) in bronchoalveolar lavage fluid (BALF) were evaluated.

RESULTS: Endotoxin decreased the PaO₂ and peripheral blood leukocyte and platelet counts. And it increased the W/D weight ratio of lung, lung injury score and leukocyte counts, percentage of PMNL, and concentrations of albumin and IL-8 in BALF. Foy^® attenuated all these changes except the decreased peripheral blood leukocyte count.

CONCLUSIONS: These findings suggest that Foy^® attenuates endotoxin-induced acute lung injury in rabbit by inhibiting neutrophil, IL-8 and platelet responses which may play a central role in sepsis related lung injury.