The combination of polymicrobial sepsis and endotoxin results in an inflammatory process that could not be predicted from the independent insults

Abstract

Background. The variable clinical profile observed in critically ill patients is the result of multiple factors. Genetic determinants have recently been shown as confounding factors in the response to injury. However, other elements, such as the environment and the type of injury, could modify this response. The objective of this investigation was to study the effect of combining insults and different genetic backgrounds on the inflammatory response. Materials. Male mice, C57BL/6J (B6) and A/J, were randomized to undergo cecal ligation and single puncture (CLP) or sham operation (SOP). After 24 h of recovery, mice were randomized again into two groups, one group was injected with bacterial lipopolysaccharide (LPS; 15 mg/kg) and the other was injected with normal saline (NS). An additional experimental group included mice that were not operated (NOP) and injected with LPS. Mice were evaluated by plasma cytokine content. Results. The combination of insults resulted in an apparent additive effect for some cytokines, such as interleukin (IL) 6. In contrast, tumor necrosis factor α (TNF-α) was considerably lower in the combined injury group with respect to injection of LPS alone. There was no relevant difference in IL-10 levels between any group, except that its decay was slower in the CLP + LPS group. Overall, cytokine levels were different between B6 and A/J mice indicating a genetic contribution. Conclusions. These results indicate that the response to stress is the combination of the type of injury and the genetic background of the subject. These observations also illustrate the difficulty in predicting the inflammatory response and underlying mechanism based on cytokine plasma levels.