Synergistic Aspects to Explain the Pathophysiology of Sepsis and Septic Shock-An Opinion

Tissue damage in post infectious sequelae is caused by a synergism between microbial and neutrophils-derived agonists: a concern for a disregard for already published data

“…However, these exciting and promising papers were soon followed by publications suggesting that high levels of circulating nuclear histones were also detected in other clinical disorders unrelated to sepsis, hinting that histones might not be the sole alarmin active agent in sepsis pathogenicity [3][4][5][6][7][8][9]. This assumption is based on a recent suggestion which re-defined sepsis as a multi-factorial synergistic phenomenon, where no single alarmin is generated which if neutralized successfully, might prevent the aftermath of severe microbial infections [9]. We also previously suggested that histone may not be a "unique evil alarmin" agent but only an additional "member of the gang" [8].…”

“…Why do we continue to pin our hopes on single antagonists when treating a multifactorial complex process like sepsis? [9].…”