Studies on the dose dependence of endotoxin-induced in vitro activation of the complement system

The dose and time dependence of in vitro endotoxin-induced activation of complement was studied in citrated pool plasma at 37 degrees C. C3 activation fragments (C3act) and the fluid-phase terminal complement complex (TCC) were used as indicators of initial and terminal activation, respectively. At 1 h marked elevation of C3act and TCC were found in plasma tested with the highest doses of endotoxin (2.10(9) and 2.10(8) ng/l). In test plasmas with 2.10(7) and 2.10(6) ng/l of endotoxin, no sign of activation was seen during the first 4 h, whereas both C3act and TCC values were increased at 12 h. In thest plasma with 2.10(5) ng/l of endotoxin and in control plasma no elevation of TCC values were seen during the observation period (24 h), whereas C3act values increased slightly and to the same extent in both at 24 h. Parallel to the increases in C3act and TCC concentrations, the functional C1 inhibitor (C1INH) values decreased. Changes in C1INH values, however, occurred with a time lag of approximately 6 h compared to the increases in C3act and TCC. Our in vitro study showed a dose-dependent endotoxin-induced activation of both the initial and the terminal part of the complement cascade evaluated by C3act and TCC.