Rabbits treated for 4 days with
cortisone to prepare for the generalized
Shwartzman reaction (GSR) were infused with
thrombin or
endotoxin. Whereas
endotoxin induced the GSR, infusion of from 120--400 U/kg of
thrombin over 1 to 2 1/2 hr failed to induce the GSR. Mean values for
fibrinogen consumption after
thrombin or
endotoxin, calculated from changes in plasma
fibrinogen concentration and plasma 125I-fibrinogen radioactivity, were as follows: for rabbits infused with
thrombin, from 43 to 61 mg/kg over a 3 hr period; for rabbits infused with
endotoxin, 58.5 mg/kg over a 6 hr period. A small peak of non-clottable
protein radioactivity, indicative of secondary fibrinolysis, was found in animals infused with
thrombin but not in animals infused with
endotoxin. A striking late rise in plasma
fibrinogen levels was noted in animals infused with
endotoxin. It was not noted in animals infused with
thrombin. This observation provides further evidence that
endotoxin stimulates
fibrinogen synthesis by mechanisms independent of intravascular clotting or fibrinolysis. The failure to produce the GSR with
thrombin in
cortisone-treated rabbits leads us to conclude that depression of reticuloendothelial cell clearance of
fibrin can not account for the preparatory effect of
cortisone for the GSR after
endotoxin.