Another example of a dilemma related to in vivo blockade of complement comes from recent studies involving mice with CLP-induced sepsis (Flierl et al. 2008 ). Use of a blocking antibody to C5a was highly protective. However, when C6 was depleted in order to prevent formation of the MAC (C5b-9), it was found that the bacterial burden in blood was much higher in CLP mice compared to complement-intact mice, consistent with the knowledge that C5b-9 has lytic activity for bacteria. Accordingly, since complement is both a potent inflammatory-inducing system as well as critically important for innate immune defenses, we need to have a much better understanding of how the system really works.