Article Commentary: Sepsis, Systemic Inflammatory Response, and Multiple Organ Dysfunction: The Mystery Continues

Abstract

Human sepsis is thought to be systemic inflammatory response syndrome (SIRS) that is activated by invasive infection. The multiple organ dysfunction syndrome (MODS) is the identified failure of critical organ function in patients that have sustained SIRS. Because SIRS and MODS are consequences of the excessive activation of inflammation, extensive research and numerous clinical trials have pursued treatments that would modify the inflammatory response. This presentation reviews the normal local mechanisms of inflammation and provides a theoretical framework for the transition of the inflammatory process to a systemic level. Clinical trials with biomodulators to block or inhibit inflammation have generally failed to improve the outcomes in patients with severe sepsis, septic shock, and MODS. The role of counter-inflammatory signaling and the newer concept of the cholinergic anti-inflammatory pathway are being investigated, and newer hypotheses are focusing upon the balancing of proinflammatory and counter-inflammatory mechanisms as important directions for newer therapies. It is concluded that failure to define novel and effective treatments reflects fundamental gaps in our understanding of inflammation and its regulation.

Anti‐inflammatory Effect of Rosmarinic Acid and an Extract of Rosmarinus officinalis in Rat Models of Local and Systemic Inflammation

“…Along with the formation of ROS, the infiltration and accumulation of polymorphonuclear leucocytes within the tissues has been considered a hallmark of the acute inflammatory response, including local inflammation hepatic ischaemia–reperfusion , acute lung injury and systemic inflammation . A prominent feature of acute inflammation is enhanced vascular permeability resulting in oedema formation.…”

Circulating Monocytes Are Not the Major Source of Plasma Cytokines in Patients With Sepsis

“…While several immunomodulatory therapies for treating sepsis, including the blocking or neutralization of pro-inflammatory cytokines, have been used in the clinic during the last two-three decades there has been little improvement in the rate of fatal outcomes in septic patients [201]. The reasons behind these failures have been suggested to stem from an incomplete understanding of the septic syndrome and by a lack of precise criteria for staging the patients' immune status [202,203].…”

“…The reasons behind these failures have been suggested to stem from an incomplete understanding of the septic syndrome and by a lack of precise criteria for staging the patients' immune status [202,203]. One argument has been that while interventions intended to reduce inflammation may be suitable during the initial phases of sepsis, such treatments should not be given to those that have moved into a secondary state dominated by anti-inflammatory mechanisms [151,169,201]. In the trials performed, patients have been categorized according to the standard criteria for sepsis, i.e.…”

Kinetics of leukocyte CD11b and CD64 expression in severe sepsis and non‐infectious critical care patients

“…Systemic inflammatory response syndrome (SIRS) is a non‐specific inflammatory reaction to various insults, including infections, burns, and major surgery . Sepsis has been defined as SIRS that occurs in response to bacterial infection .…”

“…Systemic inflammatory response syndrome (SIRS) is a non‐specific inflammatory reaction to various insults, including infections, burns, and major surgery . Sepsis has been defined as SIRS that occurs in response to bacterial infection . Early diagnosis and timely therapeutic interventions (e.g., antimicrobial treatment) are crucial to improving the outcome of sepsis patients .…”