ACTIVATED RECOMBINANT HUMAN PROTEIN-C DOES NOT ATTENUATE RECRUITMENT OF NEUTROPHILS IN RAT MODELS OF ACUTE-INFLAMMATION

It has been proposed that the reduction in mortality in animal models of sepsis by activated protein C (APC) is mediated by an antiinflammat ory property rather than the well-characterized anticoagulant action. Human recombinant APC was examined for potential antiinflammatory acti vity in the pentobarbital-anesthetized rat. In the dermal reversed pas sive Arthus model, APC (20.0 mg/kg/h, i.v.) elevated clotting time 10- fold 3 h after the Arthus challenge, at which time, the wet-weights fr om Arthus dermal samples in APC rats (120.0 +/- 1.5 mg, n = 10) did no t differ from controls (120.1 +/- 1.5 mg, n = 10) but were 30% heavier than remote noninflammed skin (92.0 +/- 2.0 mg, n = 10), indicating t hat APC treatment did not diminish tissue edema associated with immune -complex deposition. Skin-lesion myeloperoxidase (neutrophil marker en zyme) activities from APC rats were not significantly different from c ontrols but was 21-fold more than remote noninflamed skin, indicating that APC treatment did not diminish dermal recruitment of neutrophils. In the intestinal ischemia/reperfusion model, 1 h complete occlusion of the superior mesenteric artery and an additional 4 h reperfusion wa s associated with a 2.87-fold increase in lung myeloperoxidase activit y compared to sham-operated rats. APC (1.0 mg/kg/h, i.v.) did not dimi nish the elevation in this index of lung neutrophil sequestration. In conclusion, APC did not produce an antiinflammatory effect in the rat models used.