Studies on components of the plasma kallikrein-kinin system in plasma samples from normal individuals and patients with septic shock.

Components of the plasma kallikrein-kinin system were determined in plasma samples from ten healthy subjects and eight patients with septic shock. Five of the patients died. Low levels of Hageman factor, prekallikrein, and high molecular weight kininogen, together with significantly reduced concentrations of alpha 2-macroglobulin, were observed during septic shock both in patients who died and in the survivors. The patients who died also revealed a pronounced reduction of functional kallikrein inhibition determined by a chromogenic peptide substrate assay. In the survivors, however, functional kallikrein inhibition was very well preserved during septic shock, being within the range of values found in normals. Also plasma prekallikrein and C1-esterase inhibitor levels were slightly higher in the survivors than in those who died. Our results confirm that the plasma kallikrein-kinin system becomes activated during septicemia and that consumption of components of this protease system occurs. Because both C1-esterase inhibitor concentrations and functional kallikrein inhibitory activities were higher in patients who survived septic shock than in the fatal cases, our results suggest that functional inhibition of plasma kallikrein appears to play a major role in the outcome of this condition.