Both LPS-challenge model and infection model use animals that have been sensitized or primed to LPS by previous infection with BCG, increasing cytokine response and lowering the threshold lethal dose of endotoxin (61) . All animal models of sepsis and infection have been criticized for their inability to closely mimic human sepsis. The primed model is the most relevant to the study of endotoxin antagonists such as E5564. It is well known that compared with humans, unprimed rodents such as rats and mice and primates demonstrate a profound insensitivity to endotoxin, requiring endotoxin doses as high as milligrams per kilogram, whereas humans demonstrate reproducible response to endotoxin at doses as low as 2 ng/kg. This argues that either LPS contributes only weakly to the inflammatory process in animal models, or that response to infection occurs only after the level of infection is very high, representing a process different from that in more LPSsensitive species such as humans (61) .