Complement activation and its control in gram negative endotoxic shock

Serum levels of complement proteins and the plasma levels of cleavage products of C3 (C3d) and factor B (Ba) have been measured in 163 samples from patients with Gram-negative endotoxic shock. Classical pathway activation occurred as shown by reduced C4 levels and alternative pathway activation was associated with low levels of C3, properdin and increased levels of Ba. Increased activation of both classical and alternative pathways occurred during periods of shock, and during episodes of endotoxaemia which ended fatally. Levels of complement proteins and cleavage products were increased by endotoxaemia. Reduced serum levels of C1-INH, C3bINA and β1H in episodes that ended fatally, compared with episodes that were survived, suggest that serum levels of control proteins may be important in dictating the turnover of the complement system in Gram-negative endotoxic shock. Correlations between C1-INH and C1s or C4, and C3bINA or β1H, with C3, B and P, and the cleavage products Ba and C3d support this suggestion.