Pathogenesis of multiple organ dysfunction syndrome--endotoxin, inflammatory cells, and their mediators: cytokines and reactive oxygen species

Abstract

Multiple organ dysfunction syndrome (MODS) is caused by an overwhelming, uncontrolled systemic inflammatory response that is activated by a number of hostile stimuli including sepsis, hypovolemic shock, and severe trauma resulting in massive tissue injury. The indiscriminate activation of the inflammatory response due to these insults causes loss of the host's ability to localize the inflammation to the focus of the problem, leading to systemic inflammation and severe host tissue damage and subsequent MODS. While the major players, namely neutrophils, macrophages, endotoxin, cytokines, and oxidants have been known for some time, the disease processes responsible for the pathogenesis of MODS have only recently been elucidated. Our newly found knowledge has resulted in the development of novel therapeutic strategies to prevent or treat MODS, such as scavenging toxic oxygen species and inhibiting endotoxin, or cytokine production, or cytokine activity. Unfortunately, these strategies have not resulted in improved mortality rates among patients with MODS. The complex nature of the host response to severe insults combined with the fact that the host has multiple, redundant parallel systems to deal with various insults has made it difficult for clinical interventions to adequately ameliorate the disease process among patients at risk for MODS. The purpose of this article is to attempt to "dissect out" several individual components of the inflammatory response that play important roles in the development of MODS and to review some potentially beneficial approaches to combat these harmful processes.