Generation of Nitric Oxide and Reactive Oxygen Species by Neutrophils and Monocytes From Septic Patients and Association With Outcomes

Abstract

In this study, our aims were to evaluate the reactive oxygen species (ROS) and nitric oxide (NO) generation by monocytes and neutrophils from septic patients and to correlate their levels with clinical outcomes. Forty-nine septic patients and 19 healthy volunteers were enrolled in the study. The ROS and NO production was quantified in monocytes and neutrophils in whole blood by flow cytometry, constitutively, and after stimulation with Staphylococcus aureus and Pseudomonas aeruginosa. Nitric oxide production by monocytes was higher in septic patients compared with healthy volunteers for all conditions and by neutrophils at baseline, and ROS generation in monocytes and neutrophils was higher in septic patients than in healthy volunteers for all conditions. Nitric oxide production by monocytes and neutrophils was decreased at day 7 compared with that at admission (day 0) in survivors at baseline and after stimulation with S. aureus. Reactive oxygen species production by the monocytes and neutrophils was decreased in survivors at day 7 compared with day 0 under all conditions, except by neutrophils at baseline. No difference was found in NO and ROS generation by monocytes and neutrophils between day 7 and day 0 in nonsurvivors. Generation of NO and ROS by neutrophils and monocytes is increased in septic patients, and their persistence is associated with poor outcome.

CD163 and CD206 expression does not correlate with tolerance and cytokine production in LPS‐tolerant human monocytes

“…Studies of the role of monocytes in patients with severe sepsis and septic shock have revealed a hyporesponsive state characterized by low production of inflammatory cytokines in the peripheral blood cells of patients with sepsis upon restimulation in vitro (11)(12)(13). We have demonstrated that monocytes from patients with sepsis, which are hyporesponsive for the production of TNF-a (14,15), retain the ability to generate ROS and NO (1,16,17), similar to LPS-tolerant cells. Furthermore, genes belonging to the toll-like receptor (TLR) signaling pathways are dynamically modulated during sepsis (18,19) in a manner similar to that observed in LPS-tolerant human mononuclear cells (reviewed in Refs.…”

The protective effects of IgM-enriched immunoglobulin and erythropoietin on the lung and small intestine tissues of rats with induced sepsis: Biochemical and histopathological evaluation

“…Serum levels of nitric oxide and cytokines including IL-1b and TNF-a have been reported increased in patients with sepsis (Krüttgen & Rose-John, 2012;Santos et al, 2012). It was shown that in vitro synthesis of EPO in cell cultures is suppressed by TNF-a and IL-1 (Nakamura et al, 1998).…”

“…Studies have shown that emerging oxidative stress and cell damage following increased production of prostaglandins, nitric oxide, free radicals and pro-inflammatory cytokines such as tumor necrosis factor-a (TNF-a) and interleukin-1b (IL-1b) are responsible for the multiple organ failures and deaths caused by sepsis (Beutler & Poltorak, 2001;Krüttgen & Rose-John, 2012). Nitric oxide is an important source for the production of powerful free radicals and has also direct deleterious effects on cells during sepsis (Santos et al, 2012).…”

“…Nitric oxide plays a major role in the pathogenesis of sepsis (Santos et al, 2012) and EPO inhibits the activity of nitric oxide synthase (d'Uscio et al, 2007) which is responsible for the synthesis of nitric oxide. Wu et al (2010b) reported that pre-treatment with low dose (300 U/kg) EPO suppresses the release of TNF-a and IL-6 production, decreases organ damage, and improves survival rate after hemorrhagic shock in conscious rats.…”

Copper Induces Vasorelaxation and Antagonizes Noradrenaline -Induced Vasoconstriction in Rat Mesenteric Artery

“…They thought the mechanism was that DTC blocked endothelium-derived relaxing factors (EDRF) including NO. Indeed, many studies reported that NO was generated markedly in sepsis animal models and septic patients [22,23,24]. Based on that copper stimulated NO production [8,9,10], it was reasonable to speculate that copper might be involved in the vascular hyporeactivity in sepsis through enhancing NO action.…”