Pseudomonas aeruginosa Compared with Escherichia coli Produces Less Endotoxemia: Discussion (4)
As expected, radiation-induced leukopenia dramatically increased the mortality of septic shock. Uncontrolled infection due to immune suppression might have been responsible for this high mortality. Interestingly, this was not reflected by greater or more prolonged endotoxemia. This suggests that, in the setting of immune suppression (in this case radiation-induced leukopenia), levels of endotoxin that would otherwise be nonlethal may result in death. The concept of combined injury is not new, but these findings underscore the potential for complex interactions between the infecting organisms, endotoxin concentrations, and host factors that may affect outcome.
Multiple investigators support the hypothesis that release of endotoxin from Gram-negative bacteria is the principal pathogenic mechanism in septic shock. Previously we have shown that Gram-positive bacteria, in the absence of detectable endotoxin, can produce lethality and all of the cardiovascular changes of septic shock. In this study, two types of Gram-negative bacteria produced the same cardiovascular changes of septic shock, but with a negative correlation between the development of endotoxemia and clinical outcomes. It is unlikely that the development of endotoxemia in E coli sepsis was protective, suggesting that agents other than endotoxin were important pathogenic factors in Pseudomonas-infected dogs. The endotoxin concentrations in this study cannot be generalized to all strains of E coli and P aeruginosa. However, the previous data from studies of Gram-positive infection combined with data from this study strongly suggest that endotoxin is not the universal mediator of septic shock.