scholarly journals Blood and urinary cytokine balance and renal outcomes at cardiac surgery

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
William T. McBride ◽  
Mary Jo Kurth ◽  
Anna Domanska ◽  
Joanne Watt ◽  
Gavin McLean ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Inflammatory Cytokines ◽  
Clinical Utility ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Inflammatory Biomarkers ◽  
Cytokine Balance ◽  
Anti Inflammatory ◽  
Renal Hypoperfusion

Abstract Background Increased perioperative pro-inflammatory biomarkers, renal hypoperfusion and ischemia reperfusion injury (IRI) heighten cardiac surgery acute kidney injury (CS-AKI) risk. Increased urinary anti-inflammatory cytokines attenuate risk. We evaluated whether blood and urinary anti-inflammatory biomarkers, when expressed as ratios with biomarkers of inflammation, hypoperfusion and IRI are increased in CS-AKI patients. Methods Preoperative and 24-h postoperative blood and urinary pro-inflammatory and anti-inflammatory cytokines, blood VEGF and H-FABP (hypoperfusion biomarkers), and MK, a biomarker for IRI, were measured in 401 cardiac surgery patients. Pre- and postoperative concentrations of biomarkers and selected ratios thereof, were compared between non-CS-AKI and CS-AKI patients. Results Compared with non-CS-AKI, blood pro-inflammatory (pre- and post-op TNFα, IP-10, IL-12p40, MIP-1α, NGAL; pre-op IL-6; post-op IL-8, MK) and anti-inflammatory (pre- and post-op sTNFsr1, sTNFsr2, IL-1RA) biomarkers together with urinary pro-inflammatory (pre- and post-op uIL-12p40; post-op uIP-10, uNGAL) and anti-inflammatory (pre- and post-op usTNFsr1, usTNFsr2, uIL-1RA) biomarkers, were significantly higher in CS-AKI patients. Urinary anti-inflammatory biomarkers, when expressed as ratios with biomarkers of inflammation (blood and urine), hypoperfusion (blood H-FABP and VEGF) and IRI (blood MK) were decreased in CS-AKI. In contrast, blood anti-inflammatory biomarkers expressed as similar ratios with blood biomarkers were increased in CS-AKI. Conclusions The urinary anti-inflammatory response may protect against the injurious effects of perioperative inflammation, hypoperfusion and IRI. These finding may have clinical utility in bioprediction and earlier diagnosis of CS-AKI and informing future therapeutic strategies for CS-AKI patients.

Blood and urinary cytokine balance and renal outcomes at cardiac surgery

2021 ◽  
Author(s):  
Willam McBride ◽  
Mary Jo Kurth ◽  
Anna Domanska ◽  
Joanne Watt ◽  
Gavin McLean ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Inflammatory Cytokines ◽  
Clinical Utility ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Inflammatory Biomarkers ◽  
Cytokine Balance ◽  
Anti Inflammatory ◽  
Renal Hypoperfusion

Abstract BACKGROUND Increased perioperative pro-inflammatory biomarkers, renal hypoperfusion and ischemia reperfusion injury (IRI) heighten cardiac surgery acute kidney injury (CS-AKI) risk. Increased urinary anti-inflammatory cytokines attenuate risk. We evaluated whether blood and urinary anti-inflammatory biomarkers, when expressed as ratios with biomarkers of inflammation, hypoperfusion and IRI are increased in CS-AKI patients. METHODS Preoperative and 24-hour postoperative blood and urinary pro-inflammatory and anti-inflammatory cytokines, blood VEGF and H-FABP (hypoperfusion biomarkers), and MK, a biomarker for IRI, were measured in 401 cardiac surgery patients. Pre- and postoperative concentrations of biomarkers and selected ratios thereof, were compared between non-CS-AKI and CS-AKI patients. RESULTS Compared with non-CS-AKI, blood pro-inflammatory (pre- and post-op TNFα, IP-10, IL-12p40, MIP-1α, NGAL; pre-op IL-6; post-op IL-8, MK) and anti-inflammatory (pre- and post-op sTNFsr1, sTNFsr2, IL-1RA) biomarkers together with urinary pro-inflammatory (pre- and post-op uIL-12p40; post-op uIP-10, uNGAL) and anti-inflammatory (pre- and post-op usTNFsr1, usTNFsr2, uIL-1RA) biomarkers, were significantly higher in CS-AKI patients. Urinary anti-inflammatory biomarkers, when expressed as ratios with biomarkers of inflammation (blood and urine), hypoperfusion (blood H-FABP and VEGF) and IRI (blood MK) were decreased in CS-AKI. In contrast, blood anti-inflammatory biomarkers expressed as similar ratios with blood biomarkers were increased in CS-AKI. CONCLUSIONS The urinary anti-inflammatory response may protect against the injurious effects of perioperative inflammation, hypoperfusion and IRI. These finding may have clinical utility in bioprediction and earlier diagnosis of CS-AKI and informing future therapeutic strategies for CS-AKI patients.

scholarly journals Focal intra-colon cooling reduces organ injury and systemic inflammation after REBOA management of lethal hemorrhage in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Awadhesh K. Arya ◽  
Kurt Hu ◽  
Lalita Subedi ◽  
Tieluo Li ◽  
Bingren Hu
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Balloon Catheter ◽  
Organ Injury ◽  
Upper Body ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

AbstractResuscitative endovascular balloon occlusion of the aorta (REBOA) is a lifesaving maneuver for the management of lethal torso hemorrhage. However, its prolonged use leads to distal organ ischemia–reperfusion injury (IRI) and systemic inflammatory response syndrome (SIRS). The objective of this study is to investigate the blood-based biomarkers of IRI and SIRS and the efficacy of direct intestinal cooling in the prevention of IRI and SIRS. A rat lethal hemorrhage model was produced by bleeding 50% of the total blood volume. A balloon catheter was inserted into the aorta for the implementation of REBOA. A novel TransRectal Intra-Colon (TRIC) device was placed in the descending colon and activated from 10 min after the bleeding to maintain the intra-colon temperature at 37 °C (TRIC37°C group) or 12 °C (TRIC12°C group) for 270 min. The upper body temperature was maintained at as close to 37 °C as possible in both groups. Blood samples were collected before hemorrhage and after REBOA. The organ injury biomarkers and inflammatory cytokines were evaluated by ELISA method. Blood based organ injury biomarkers (endotoxin, creatinine, AST, FABP1/L-FABP, cardiac troponin I, and FABP2/I-FABP) were all drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated these increased organ injury biomarkers. Plasma levels of pro-inflammatory cytokines TNF-α, IL-1b, and IL-17F were also drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated the pro-inflammatory cytokines. In contrast, TRIC12°C significantly upregulated the levels of anti-inflammatory cytokines IL-4 and IL-10 after REBOA. Amazingly, the mortality rate was 100% in TRIC37°C group whereas 0% in TRIC12°C group after REBOA. Directly cooling the intestine offered exceptional protection of the abdominal organs from IRI and SIRS, switched from a harmful pro-inflammatory to a reparative anti-inflammatory response, and mitigated mortality in the rat model of REBOA management of lethal hemorrhage.

scholarly journals Reducing Inflammatory Cytokine Production from Renal Collecting Duct Cells by Inhibiting GATA2 Ameliorates Acute Kidney Injury

2017 ◽  
Vol 37 (22) ◽  
Author(s):  
Lei Yu ◽  
Takashi Moriguchi ◽  
Hiroshi Kaneko ◽  
Makiko Hayashi ◽  
Atsushi Hasegawa ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Ischemia Reperfusion Injury ◽  
Collecting Duct ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Cytokine Gene Expression ◽  
Renal Tubular Cell

ABSTRACT Acute kidney injury (AKI) is a leading cause of chronic kidney disease. Proximal tubules are considered to be the primary origin of pathogenic inflammatory cytokines in AKI. However, it remains unclear whether other cell types, including collecting duct (CD) cells, participate in inflammatory processes. The transcription factor GATA2 is specifically expressed in CD cells and maintains their cellular identity. To explore the pathophysiological function of GATA2 in AKI, we generated renal tubular cell-specific Gata2 deletion (G2CKO) mice and examined their susceptibility to ischemia reperfusion injury (IRI). Notably, G2CKO mice exhibited less severe kidney damage, with reduced granulomacrophagic infiltration upon IRI. Transcriptome analysis revealed that a series of inflammatory cytokine genes were downregulated in GATA2-deficient CD cells, suggesting that GATA2 induces inflammatory cytokine expression in diseased kidney CD cells. Through high-throughput chemical library screening, we identified a potent GATA inhibitor. The chemical reduces cytokine production in CD cells and protects the mouse kidney from IRI. These results revealed a novel pathological mechanism of renal IRI, namely, that CD cells produce inflammatory cytokines and promote IRI progression. In injured kidney CD cells, GATA2 exerts a proinflammatory function by upregulating inflammatory cytokine gene expression. GATA2 can therefore be considered a therapeutic target for AKI.

scholarly journals P0527AROLE OF PROMOTING INFLAMMATION OF KLF6 IN ACUTE KIDNEY INURY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Dan Li ◽  
Chenyu Li ◽  
Yan Xu
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tnf Α ◽  
Public Dataset ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine ◽  
Pro Inflammatory Cytokines

Abstract Background and Aims Acute kidney injury (AKI), commonly appeared in cardiac arrest, surgery and kidney transplantation which involved in ischemia-reperfusion (IR) injury of kidney. However, the mechanisms underlying inflammatory response in IR AKI is still unclear. Method Public dataset showed kruppel-like factor 6 (KLF6) was significantly highly expressed (P<0.05) in AKI, implies KLF6 might be associated with AKI. To evaluate the mechanism of KLF6 on IR AKI, 30 rats were randomly divided into sham and IR group, and were sacrificed at 0 h, 3 h, 6 h, 12 h or 24 h after IR. Results The results showed KLF6 expression was peaking at 6 h after IR, and the expression of pro-inflammatory cytokines MCP-1 and TNF-α were increased both in serum and kidney tissues after IR, while anti-inflammatory cytokine IL-10 was decreased after IR. Furthermore, in vitro results showed KLF6 knock-down reduced the pro-inflammatory cytokines expression and increased the anti-inflammatory cytokines expression. Conclusion These results suggest that (1) KLF6 might be a novel biomarker for early diagnosis of AKI and (2) targeting KLF6 expression may offer novel strategies to protect kidneys from IR AKI Figure KLF6, AKI, Control Inflammation

scholarly journals Poly(I:C)-Induced Mesenchymal Stem Cells Protect the Kidney Against Ischemia/Reperfusion Injury via the TLR3/PI3K Pathway

2021 ◽  
Vol 8 ◽  
Author(s):  
Tian Chen ◽  
Yamei Jiang ◽  
Shihao Xu ◽  
Yin Celeste Cheuk ◽  
Jiyan Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Renal Function ◽  
Inflammatory Cytokines ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Pi3k Pathway ◽  
Poly I:C ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory

Objective: To investigate the effect and protective mechanism of mesenchymal stem cell subpopulations on acute kidney injury by establishing a mouse model of renal ischemia-reperfusion injury.Methods: Male C57BL/6 mice were randomly divided into five groups, namely, sham-operation group and those treated with normal saline, untreated mesenchymal stem cells, mesenchymal stem cells treated with lipopolysaccharide (LPS, pro-inflammatory phenotype) and mesenchymal stem cells treated with polyinosinic-polycytidylic acid (poly[I:C], anti-inflammatory phenotype) respectively. The renal function, histopathological damage, circulating inflammation levels and antioxidant capacity of mice were evaluated. The PI3 kinase p85 (PI3K) inhibitor was added into the conventional mesenchymal stem cell cultures in vitro to observe its effects on the secretion of anti-inflammatory cytokines.Results: Mesenchymal stem cells treated with poly(I:C) (anti-inflammatory phenotype) could effectively reduce serum creatinine and blood urea nitrogen, attenuate histopathological damage and apoptosis level, decrease the level of circulating pro-inflammatory cytokines and increase the level of circulating anti-inflammatory cytokines, enhance peroxidase activity and reduce malondialdehyde content at each time point. After the addition of the PI3K inhibitor, the mRNA expression and protein secretion of indoleamine 2,3-dioxygenase 1 and heme oxygenase 1 of various mesenchymal stem cells were significantly reduced, and that of mesenchymal stem cells treated with poly(I:C) (anti-inflammatory phenotype) was more obvious.Conclusions: Polyriboinosinic-polyribocytidylic acid (poly[I:C]), a synthetic double-stranded RNA, whose pretreatment induces mesenchymal stem cells to differentiate into the anti-inflammatory phenotype. Anti-inflammatory mesenchymal stem cells induced by poly(I:C) can better protect renal function, alleviate tissue damage, reduce circulating inflammation levels and enhance antioxidant capacity, and achieve stronger anti-inflammatory effects through the TLR3/PI3K pathway.

scholarly journals Neuroprotective and Anti-Inflammatory Effect of Pterostilbene Against Cerebral Ischemia/Reperfusion Injury via Suppression of COX-2

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenjun Yan ◽  
Dongqing Ren ◽  
Xiaoxue Feng ◽  
Jinwen Huang ◽  
Dabin Wang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Inflammatory Cytokines ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Polymorphonuclear Leucocyte ◽  
The Body ◽  
Cox 2 ◽  
Anti Inflammatory

Background: The incidence of cerebral ischemia disease leading cause of death in human population worldwide. Treatment of cerebral ischemia remains a clinical challenge for researchers and mechanisms of cerebral ischemia remain unknown. During the cerebral ischemia, inflammatory reaction and oxidative stress plays an important role. The current investigation scrutinized the neuroprotective and anti-inflammatory role of pterostilbene against cerebral ischemia in middle cerebral artery occlusion (MCAO) rodent model and explore the underlying mechanism.Methods: The rats were divided into following groups viz., normal, sham, MCAO and MCAO + pterostilbene (25 mg/kg) group, respectively. The groups received the oral administration of pterostilbene for 30 days followed by MCAO induction. The neurological score, brain water content, infarct volume and Evan blue leakage were estimated. Hepatic, renal, heart, inflammatory cytokines and inflammatory mediators were estimated.Results: Pterostilbene treatment significantly (p < 0.001) improved the body weight and suppressed the glucose level and brain weight. Pterostilbene significantly (p < 0.001) reduced the hepatic, renal and heart parameters. Pterostilbene significantly (p < 0.001) decreased the level of glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and decreased the level of malonaldehyde (MDA), 8-Hydroxy-2′-deoxyguanosine (8-OHdG). Pterostilbene significantly (p < 0.001) inflammatory cytokines and inflammatory parameters such as cyclooxygenase-2 (COX-2), inducible nitric oxidase synthase (iNOS) and prostaglandin (PGE2). Pterostilbene significantly (p < 0.001) down-regulated the level of metalloproteinases (MMP) such as MMP-2 and MMP-9. Pterostilbene suppressed the cellular swelling, cellular disintegration, macrophage infiltration, monocyte infiltration and polymorphonuclear leucocyte degranulation in the brain.Conclusion: In conclusion, Pterostilbene exhibited the neuroprotective effect against cerebral ischemia in rats via anti-inflammatory mechanism.

Abstract 2269: Exogenous Sulfide Limits Inflammation in Response to Myocardial Ischemia - Reperfusion Injury

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Neel R Sodha ◽  
Richard T Clements ◽  
Jun Feng ◽  
Yuhong Liu ◽  
Cesario Bianchi ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
Inflammatory Cytokines ◽  
Sodium Sulfide ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Treated Group ◽  
Area At Risk ◽  
Microvascular Reactivity ◽  
Anti Inflammatory

Introduction : Hydrogen sulfide (H 2 S) is produced endogenously in response to myocardial ischemia and thought to be cardioprotective. The mechanism underlying this protection has yet to be fully elucidated, but may be related to the ability of sulfide to limit inflammation. This study investigates the cardioprotection provided by exogenous H 2 S, generated as sodium sulfide, and its potential anti-inflammatory mechanism of action. Methods : The mid-LAD coronary artery in 12 Yorkshire swine was acutely occluded for 60 min, followed by reperfusion for 120 min. Controls (6) received placebo, and treatment animals (6) received sulfide 10 min prior to reperfusion. Hemodynamic, global, and regional functional measurements were obtained. Evans blue and TTC staining identified the area at risk (AAR) and infarction. Coronary microvascular reactivity was assessed. Tissue was assayed for myeloperoxidase (MPO) activity and inflammatory cytokines. Results : Pre-I/R hemodynamics were similar between groups, whereas post-I/R mean arterial pressure (mmHg) was reduced by 28.7±5.0 in controls vs. 6.7±6.2 in treatment animals (p<0.05). +LV dP/dt (mmHg/sec) was reduced by 1325±455 in controls vs. 416±207 in treatment animals (p<0.05). Segmental shortening in the AAR was better in treatment animals. Infarct size (% of AAR) in controls was 41.0±7.8% vs. 21.2±2.5% in the treated group (p<0.05). Tissue levels of IL-6, IL-8, and TNFα (see Table ) and MPO activity decreased in the treatment group (0.0025±0.003 vs. control 0.0397±0.016 units/mg protein (p<0.05)). Treated animals demonstrated improved microvascular reactivity. Conclusions : Sodium sulfide provides significant protection in response to I/R injury, improving myocardial function, reducing infarct size, and improving coronary microvascular reactivity, potentially through its anti-inflammatory properties. Exogenous sulfide may have therapeutic utility in clinical settings in which I/R injury is encountered. Myocardial Levels of Inflammatory Cytokines

scholarly journals KIM-1-mediated anti-inflammatory activity is preserved by MUC1 induction in the proximal tubule during ischemia-reperfusion injury

2021 ◽  
Author(s):  
Mohammad M Al-bataineh ◽  
Carol L Kinlough ◽  
Zaichuan Mi ◽  
Edwin Kerry Jackson ◽  
Stephanie Mutchler ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Mdck Cells ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Inflammatory Activity ◽  
Proximity Ligation Assay ◽  
Mucin 1 ◽  
Anti Inflammatory

Cell-associated kidney injury molecule-1 (KIM-1) exerts an anti-inflammatory role following kidney injury by mediating efferocytosis and downregulating the NF-kB pathway. KIM-1 cleavage blunts its anti-inflammatory activities. We reported that Mucin 1 (MUC1) is protective in a mouse model of ischemia-reperfusion injury (IRI). As both KIM-1 and MUC1 are induced in the proximal tubule (PT) during IRI and are ADAM17 substrates, we tested the hypothesis that MUC1 protects KIM-1 activity. Muc1 KO mice and wild-type (WT) littermates were subjected to IRI. KIM-1, MUC1 and ADAM17 levels (and signaling pathways) were assessed by immunoblotting. PT localization was assessed by confocal microscopy and in situ proximity ligation assay. Findings were extended using human kidneys and urine, and KIM-1-mediated efferocytosis assays in mouse PT cultures. In response to tubular injury in mouse and human kidneys, we observed induction and co-expression of KIM-1 and MUC1 in the PT. Compared to WT, Muc1 KO mice had higher urinary KIM-1 and lower kidney KIM-1. KIM-1 was apical in PT of WT kidneys, but predominately with luminal debris in Muc1 KO mice. Efferocytosis was reduced in Muc1 KO PT cultures when compared to WT cells, while inflammation was increased in Muc1 KO kidneys when compared to WT mice. MUC1 was cleaved by ADAM17 in PT cultures, and blocked KIM-1 shedding in MDCK cells. We conclude that KIM-1-mediated efferocytosis and thus anti-inflammatory activity during IRI is preserved in the injured kidney by MUC1 inhibition of KIM-1 shedding.

scholarly journals Laminarin Pretreatment Provides Neuroprotection against Forebrain Ischemia/Reperfusion Injury by Reducing Oxidative Stress and Neuroinflammation in Aged Gerbils

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 213 ◽  
Author(s):  
Joon Ha Park ◽  
Ji Hyeon Ahn ◽  
Tae-Kyeong Lee ◽  
Cheol Woo Park ◽  
Bora Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Pyramidal Neurons ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Forebrain Ischemia ◽  
Ca1 Pyramidal Neurons ◽  
Before And After ◽  
Anti Inflammatory

Laminarin is a polysaccharide isolated from brown algae that has various biological and pharmacological activities, such as antioxidant and anti-inflammatory properties. We recently reported that pretreated laminarin exerted neuroprotection against transient forebrain ischemia/reperfusion (IR) injury when we pretreated with 50 mg/kg of laminarin once a day for seven days in adult gerbils. However, there have been no studies regarding a neuroprotective effect of pretreated laminarin against IR injury in aged animals and its related mechanisms. Therefore, in this study, we intraperitoneally inject laminarin (50 mg/kg) once a day to aged gerbils for seven days before IR (5-min transient ischemia) surgery and examine the neuroprotective effect of laminarin treatment and the mechanisms in the gerbil hippocampus. IR injury in vehicle-treated gerbils causes loss (death) of pyramidal neurons in the hippocampal CA1 field at five days post-IR. Pretreatment with laminarin effectively protects the CA1 pyramidal neurons from IR injury. Regarding the laminarin-treated gerbils, production of superoxide anions, 4-hydroxy-2-nonenal expression and pro-inflammatory cytokines [interleukin(IL)-1β and tumor necrosis factor-α] expressions are significantly decreased in the CA1 pyramidal neurons after IR. Additionally, laminarin treatment significantly increases expressions of superoxide dismutase and anti-inflammatory cytokines (IL-4 and IL-13) in the CA1 pyramidal neurons before and after IR. Taken together, these findings indicate that laminarin can protect neurons from ischemic brain injury in an aged population by attenuating IR-induced oxidative stress and neuroinflammation.

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