Novel Identification of Myeloid-Derived Suppressor Cells in Children With Septic Shock

Abstract

Immunoparalysis in children with septic shock is associated with increased risk of nosocomial infections and death. Myeloid-derived suppressor cells (MDSCs) potently suppress T cell function and may perpetuate immunoparalysis. Our goal was to test the hypothesis that children with septic shock would demonstrate increased proportions of MDSCs and impaired immune function compared with healthy controls.DESIGN: Prospective observational study. SETTING: Fifty-four bed PICU in a quaternary-care children's hospital. PATIENTS:Eighteen children with septic shock and thirty age-matched healthy children. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood and stained for cell surface markers to identify MDSCs by flow cytometric analysis, including granulocytic and monocytic subsets. Adaptive and innate immune function was measured by ex vivo stimulation of whole blood with phytohemagglutinin-induced interferon (IFN) γ production and lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α production, respectively. Prolonged organ dysfunction (OD) was defined as greater than 7 days. Children with septic shock had a higher percentage of circulating MDSCs, along with lower LPS-induced TNFα and phytohemagglutinininduced IFNγ production capacities, compared with healthy controls. A cut-off of 25.2% MDSCs of total PBMCs in initial samples was optimal to discriminate children with septic shock who went on to have prolonged OD, area under the curve equal to 0.86. Children with prolonged OD also had decreased TNFα production capacity over time compared with those who recovered more quickly (p = 0.02). CONCLUSIONS:This article is the first to describe increased MDSCs in children with septic shock, along with an association between early increase in MDSCs and adverse OD outcomes in this population. It remains unclear if MDSCs play a causative role in sepsis-induced immune suppression in children. Additional studies are warranted to establish MDSC as a potential therapeutic target.

Clinical value of CVP+VIVC in predicting fluid resuscitation in patients with septic shock

“…A ventricle is in the plateau phase of the Frank-Starling curve, and even increasing cardiac preload with fluids does not noticeably increase cardiac output. Previous study has found that patients with volume responsiveness account for only 40-50% of hemodynamically unstable patients 26 . As a result, excessive fluid replacement can cause pulmonary oedema and heart failure, affecting the metabolism and oxygenation of organs and tissues, aggravating the patient's condition and ultimately leading to increased mortality 27 .…”

“…More attention should be paid to the cardiac function to evaluate the volume responsiveness. If both the left and right ventricles are in the ascending phase of the Frank-Starling curve, there is volume responsiveness as OC will increase with increased cardiac preload after fluid resuscitation 25 . A ventricle is in the plateau phase of the Frank-Starling curve, and even increasing cardiac preload with fluids does not noticeably increase cardiac output.…”

Comparison of whole blood cytokine immunoassays for rapid, functional immune phenotyping in critically ill patients with sepsis

“…, opting for 500 pg/ml LPS from Salmonella abortus equi, as opposed to their 2.5 ng/ml. This decision was informed by prior studies from Hall and colleagues [ 28 – 33 ]. Our results suggest a consistent link between LPS-induced TNF production and patient mortality.…”

Alpha-Fetoprotein: A Revolutionary Anti-Cancer Drug

“…AFP with glucocorticoids or indomethacin stimulate MDSCs' activity. That establishes MDSC as a potential therapeutic target for immune suppression during ADs, transplantation, trauma, septic shock 73 , and other conditions.…”