THE DOSE DEPENDENCE OF ENDOTOXIN INDUCED ACTIVATION OF THE PLASMA CONTACT SYSTEM. AN IN VITRO STUDY

Abstract

The dose and time dependence of endotoxin induced activation of the plasma contact system was studied in citrated plasma incubated at 37,4 °C. During the first six hours no significant changes were seen. At 12 hours markedly elevated plasma kalli-krein (KK) activity was found in plasma tested with the highest doses of endotoxin (2000 and 200 γg/ml). Corresponding to the elevated KK activity reductions of both plasma prekallekrein (PKK) and functional kallekrein inhibition (KKI) were seen. Hageman factor (FXII) values determined immunologically were also reduced parallel to the decreases of PKK and KKI. Changes in high molecular weight kininogen (HMwK) values were seen as wellIn plasma tested with doses of endotoxin lower than 200γg/ml no sign of activation was seen at 12 hours. At 24 hours, however, increased KK activity and decreased KKI and PKK values were seen in plasma incubated with 20 γg/ml of endotoxin. In test plasma with endotoxin concentrations of 2 and 0,6 γg/ml we found . sign of activation in 7 of 8 test tubes using 2 γg/ml and in 2 of 6 test tubes using 0,6γg/ml. In test plasma with the lowest dose of endotoxin (2,0 γg/ml) and in control plasma no changes in either KK activity, KKI, PKK, FXII or HMwK values were found at 24 hoursThe study shows thaf- endotoxin induced activation of the contact system in citrated plasma is a slow process which is both time and dose