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Giamarellos‐Bourboulis, Evangelos J.; Routsi, Christina; Plachouras, Diamantis; Markaki, Vasiliki; Rosario, Maria; Zervakis, Dimitrios; Koussoulas, Vassilios; Orfanos, Stylianos E.; Κοτανίδου, Αναστασία; Armaganidis, Apostolos; Roussos, Charis; Giamarellou, Helen

doi:10.1186/cc4921

Cited by 46 publications

(21 citation statements)

References 17 publications

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“…Additionally, this group had lower serum IL-6, IL-8 and TNF-a levels at the end of a seven-day monitoring period. The authors suggested that monocytes undergoing apoptosis may lose ability to release proinflammatory cytokines, thus inhibiting a hyperactive immune response and contributing to their survival outcome [21]. In the present study no IL-6 responses were detected in plasma.…”

Section: Discussioncontrasting

confidence: 63%

“…Immune responses of 31 TD, 2 TD and 0.4 TD treatment groups before and after HS and resuscitation TD (n ¼ 6) 1.10 AE 0.11 1.12 AE 0 21. 1.05 AE 0.15 %CD25þ lymphocytes 31 TD (n ¼ 10) 9.15 AE 2.90 8.68 AE 1.99 10.03 AE 2.28 2 TD (n ¼ 9) 13.5 AE 3.90 10.33 AE 1.90 12.1 AE 2.23 0.4 TD (n ¼ 9) 9.98 AE 2.18 12.41 AE 3.62 12.28 AE 2.55 CD11b on lymphocytes 31 TD (n ¼ 10…”

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confidence: 99%

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Immune Effects of Decreasing Low-Molecular Weight Hemoglobin Components of Hemoglobin-Based Oxygen Carriers (HBOC) in a Swine Model of Severe Controlled Hemorrhagic Shock

VanderMolen

Malkevich

Philbin

et al. 2007

Artificial Cells, Blood Substitutes, and Biotechnology

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Hemoglobin-based oxygen carriers (HBOCs) show potential as safe, efficacious, pre-hospital resuscitation fluids. The major criticism of HBOC-201 is its vasoactive property, attributed partially to low-molecular weight (low-MW) tetrameric/dimeric (TD) hemoglobin (Hb) in HBOC solution. Here we sought to determine whether resuscitation with decreasing concentrations of low-MW Hb component of HBOC affects immune responses in hemorrhagic swine. 28 anesthetized swine underwent a soft muscle crush and controlled hemorrhage of 55% blood volume, followed by resuscitation with HBOC containing 31%, 2%, or 0.4% low-MW Hb in four 10 ml/kg infusions at 20, 30, 45 and 60 minutes before hospital arrival at 75 minutes. IL-10, cell activation and adhesion markers and CD4:CD8 ratio remained unchanged in all 3 groups compared to baseline. Leukocyte apoptosis was equally elevated across all groups. Purification from 31% to 0.4% low-MW Hb in HBOC solution did not alter immune effects in a swine model of severe controlled hemorrhagic shock.

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Section: Discussioncontrasting

confidence: 63%

mentioning

confidence: 99%

Immune Effects of Decreasing Low-Molecular Weight Hemoglobin Components of Hemoglobin-Based Oxygen Carriers (HBOC) in a Swine Model of Severe Controlled Hemorrhagic Shock

VanderMolen

Malkevich

Philbin

et al. 2007

Artificial Cells, Blood Substitutes, and Biotechnology

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show abstract

“…It is likely that this phenomenon is related to reduced macrophage performance and survival in WT mice subjected to CLP, since high NO levels during sepsis can impair macrophage function through a reduction in cytokine production and macrophage apoptosis [22,23]. On the other hand, NO also induces neutrophil activation at the site of infection, triggering a proinflammatory response [24], which is likely to increase sepsis severity.…”

Section: Discussionmentioning

confidence: 99%

The P2X7 Receptor Contributes to the Development of the Exacerbated Inflammatory Response Associated with Sepsis

Santana¹,

Benjamim²,

Martinez³

et al. 2015

J Innate Immun

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Background: Sepsis is associated with high mortality rates in intensive care units worldwide and represents a systemic inflammatory response to infection. P2X7 is an ionotropic purine receptor with known proinflammatory activity. Here, we investigated the role of the P2X7 receptor in sepsis induced by cecal ligation and puncture (CLP). Methods: Wild-type (WT) and P2X7KO (P2X7 null) mice were subjected to CLP and their survival was monitored for 7 days. Blood, peritoneal wash and lungs were collected 24 h after CLP and used to measure bacterial load, immune cell infiltration, nitric oxide (NO), cytokine levels, and peritoneal cell death and to assess lung injury. Results: P2X7KO mice showed significantly increased survival 7 days after CLP (30% compared to 60% in WT animals) accompanied by an overall attenuated inflammatory response, with decreased cell recruitment to the peritoneum, no or limited increases in the levels of NO and proinflammatory cytokines (IL-1β, IL-6, IL-12, IL-17, and IL-4), reduced peritoneal cell apoptosis, and less pronounced lung infiltration and morphological changes. Conclusions: Our data show the P2X7 receptor is required for the development of the inflammatory response associated with sepsis and support the notion that P2X7 receptor is a valid therapeutic target against inflammatory diseases.

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“…Using similar cell-based annexin V-FITC assays, other investigators have reported varying percentages in the degree of monocyte apoptosis seen in similar groups of patients. Bilbault et al [21] reported 15.7% monocyte apoptosis in severe sepsis patients, Giamarellos-Bourboulis et al [22] reported 27.6-55.4% monocyte apoptosis in septic shock patients, and Weiss et al [23] reported a range of 10-20% in a mix of severe sepsis and septic shock patients. Our finding of apoptosis at a median range of 14-18% is in keeping with some of these observations.…”

Section: Discussionmentioning

confidence: 99%

High Cut-Off Hemofiltration versus Standard Hemofiltration: A Pilot Assessment of Effects on Indices of Apoptosis

et al. 2014

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Objectives: To measure plasma pro-apoptotic and pro-necrotic activity in severe acute kidney injury (AKI) patients within a randomized controlled trial of continuous veno-venous hemofiltration with high cut-off filters (CVVH-HCO) versus standard filters (CVVH-Std). Methods: We measured pro-apoptotic and pro-necrotic plasma activity by trypan blue exclusion cell viability assay, detection of DNA fragmentation, and by determination of caspase-3 activity and annexin V-based apoptosis and necrosis detection assay. Results: Compared to no apoptosis or necrosis after incubation with healthy plasma, 14-18% of cells showed apoptosis and 4-8% showed necrosis after incubation with plasma from AKI patients. When comparing different measures of pro-apoptotic or pro-necrotic activity, CVVH-HCO and CVVH-Std showed no differential effects on such activity, which remained high over the first 3 days of treatment. However, using annexin V-FITC, there was a significant drop in pro-apoptotic activity across the filter for the CVVH-HCO group (p = 0.043) but not for the CVVH-Std group (p = 0.327) and a significant difference between the two groups (CVVH-HCO vs. CVVH-Std p = 0.006). Conclusions: Patients with severe AKI have increased pro-apoptotic and pro-necrotic activity. Although on single-pass effect assessment, CVVH-HCO was superior to CVVH-Std in decreasing annexin V-FITC-assessed pro-apoptotic activity, there was no overall attenuation of such activity during the first 3 days of treatment.

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Abstract: Introduction Based on the central role of the triggering of monocytes for the initiation of the septic cascade, it was investigated whether apoptosis of blood monocytes in septic patients is connected to their final outcome.

Cited by 46 publications

References 17 publications

Immune Effects of Decreasing Low-Molecular Weight Hemoglobin Components of Hemoglobin-Based Oxygen Carriers (HBOC) in a Swine Model of Severe Controlled Hemorrhagic Shock

Immune Effects of Decreasing Low-Molecular Weight Hemoglobin Components of Hemoglobin-Based Oxygen Carriers (HBOC) in a Swine Model of Severe Controlled Hemorrhagic Shock

The P2X7 Receptor Contributes to the Development of the Exacerbated Inflammatory Response Associated with Sepsis

High Cut-Off Hemofiltration versus Standard Hemofiltration: A Pilot Assessment of Effects on Indices of Apoptosis

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