EVALUATION OF ENDOTOXIN MODELS FOR THE STUDY OF SEPSIS

摘要: Many strategies have been proposed for the treatment of sepsis, and most modalities failed in clinical trials. previous protocols called blocking activity a single, clearly defined mediator. The underlying hypothesis was that sepsis induced specific mediator then caused organ injury death. This simple, linear reasoning frequently based on cytokines were using endotoxin models sepsis. widely used to study pathophysiology felt adequately reproduce full spectrum inflammatory changes observed patients with Based mortality hematologic changes, these assumptions appeared justified. As examined more closely, directly compared focus infection accurately portray it became apparent did not mimic patient In models, explosive release into circulating blood volume reproducibly found regardless species studied (human, primate, pig, rat, or mouse). lead series anticytokine trials, all which failed. cytokine response such as by cecal ligation puncture, be similar When inhibitor puncture model, they also generally lack efficacy. Compounds shown effective at reducing should re-evaluated clinically relevant