Lipopolysaccharide- and Superantigen-Modulated Superoxide Production and Monocyte Hyporesponsiveness to Activating Stimuli in Sepsis

Abstract

The effects of acute and prior exposure to lipopolysaccharide (LPS) and staphylococcal enterotoxin B (SEB) on superoxide release by monocytes were examined in control subjects and in patients with sepsis and septic shock during the acute stage and recovery. High doses of LPS, PMA (phorbol 12-myristate 13-acetate), and SEB stimulated monocyte superoxide release in control subjects (P < 0.05). Pretreatment of normal monocytes with these doses of LPS, PMA, and SEB induced significant hyporesponsiveness to subsequent challenge (P < 0.01), and evidence of cross-tolerance was observed. Monocytes isolated from patients with sepsis and septic shock demonstrated high spontaneous superoxide release compared with those of control subjects (P < 0.05). Stimulation of patient monocytes with LPS or SEB resulted in less superoxide production than that spontaneously released by controls (P < 0.01). In patients recovering from their initial infection, spontaneous superoxide release was less than that released during acute stage. In addition, the superoxide release in response to the same stimuli was significantly increased when compared with release during the acute stage (P < 0.05). These data demonstrate that both LPS and SEB induce hyporesponsiveness to LPS- or SEB-stimulated superoxide release. A similar pattern of hyporesponsiveness was observed during sepsis that may represent a mechanism for modulating the inflammatory response during severe infections.

Frontline Science: Endotoxin-induced immunotolerance is associated with loss of monocyte metabolic plasticity and reduction of oxidative burst

“…Oxidative responses are classically linked to the early hyperinflammatory phase of sepsis and associate with increased organ damage . However, during monocyte immunotolerance, impaired ROS production was observed, and attenuated superoxide production was reported after ex vivo restimulation of monocytes from septic patients . In line with this, we observed impaired oxidative burst in immunotolerant monocytes, both ex vivo and in vitro.…”

Predicting Organ Dysfunction in Septic and Critically Ill Patients: A Prospective Cohort Study Using Rapid Ex Vivo Immune Profiling

“…To determine the required sample size, we referenced previous studies that investigated the association between LPS-induced cytokine production and sepsisrelated organ dysfunction (31)(32)(33)(34). These studies enrolled between 21 and 102 critically ill patients.…”

Hydroethanolic Extract of Buchholzia coriacea Seeds Alleviates LPS Induced Liver Injury in Rat via Antioxidant and Anti-inflammatory Actions

“…LPS -induced acute liver injury is frequently accompanied by a high level of oxidative stress due to the production of ROS and RNS such as: Ÿ , H 2 O 2 , NO and resulting in depletion of hepatic redox regulatory molecules most importantly, the GSH [43,45,46]. The NADPH Oxidases (NOXs) have been identified as vital components involved in the initiation of the immune response to bacterial LPS [47].…”