Cardiovascular dysfunction caused by cecal ligation and puncture is attenuated in CD8 knockout mice treated with anti-asialoGM1

2005 ◽  
Vol 289 (2) ◽  
pp. R478-R485 ◽  
Author(s):  
Weike Tao ◽  
Victor T. Enoh ◽  
Cheng Y. Lin ◽  
William E. Johnston ◽  
Peng Li ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Arterial Pressure ◽  
Systemic Vascular Resistance ◽  
Knockout Mice ◽  
Myocardial Function ◽  
Cecal Ligation ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Cecal Ligation And Puncture ◽  
Wild Type

The present study was designed to assess hemodynamics and myocardial function at 18 h after injury caused by cecal ligation and puncture (CLP) in CD8-knockout mice treated with anti-asialoGM1 (CD8KO/αAsGM1 mice). Arterial pressure was measured by carotid artery cannulation, and left ventricular pressure-volume measurements were obtained by use of a 1.4-Fr conductance catheter. Blood acid-base balance and indexes of hepatic, renal, and pulmonary injury were also measured. CD8KO/αAsGM1 mice exhibited higher mean arterial pressure and increased systemic vascular resistance compared with wild-type mice. Cardiac output was significantly decreased in wild-type, but not CD8KO/αAsGM1, mice compared with sham controls. Myocardial function was better preserved in CD8KO/αAsGM1 mice as indicated by less impairment of left ventricular pressure development over time, time varying maximum elastance, end-systolic pressure-volume relationship, and preload recruitable stroke work. The impairment in myocardial function was associated with induction of proinflammatory cytokine mRNAs in the hearts of wild-type mice. The hemodynamic derangements in wild-type mice were coupled with significant metabolic acidosis and elevated serum creatinine levels. Overall, this study shows that cardiovascular collapse and shock characterized by hypotension, myocardial depression, low systemic vascular resistance, and metabolic acidosis occurs after CLP in wild-type mice but is attenuated in CD8KO/αAsGM1 mice. These observations likely explain, in part, the previously observed survival advantage of CD8KO/αAsGM1 mice following CLP.

β2-Microglobulin knockout mice treated with anti-asialoGM1 exhibit improved hemodynamics and cardiac contractile function during acute intra-abdominal sepsis

2004 ◽  
Vol 286 (3) ◽  
pp. R569-R575 ◽  
Author(s):  
Weike Tao ◽  
Edward R. Sherwood
Keyword(s):  
Arterial Pressure ◽  
Systemic Vascular Resistance ◽  
Vascular Resistance ◽  
Knockout Mice ◽  
Contractile Function ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Wild Type ◽  
Cardiac Contractile Function ◽  
Cardiac Contractile

We previously showed that β2-microglobulin knockout mice treated with anti-asialoGM1 (β2M/αAsGM1 mice) exhibit less hypothermia, reduced production of proinflammatory cytokines, less metabolic acidosis, and improved survival after cecal ligation and puncture (CLP) compared with wild-type mice. The present study was designed to assess hemodynamics and left ventricular contractility at 18 h after CLP. Arterial pressure was measured by carotid artery cannulation, and left ventricular pressure-volume loops were obtained by insertion of a 1.4-F conductance catheter into the left ventricle. Heart rate, stroke volume, and cardiac output were not significantly different between wild-type and β2M/αAsGM1 mice after CLP. However, β2M/αAsGM1 mice exhibited improved mean arterial pressure and systemic vascular resistance compared with wild-type mice. Myocardial function was also better preserved in β2M/αAsGM1 mice as indicated by improved left ventricular pressure development over time, time-varying maximum elastance, endsystolic pressure-volume relationship, and preload recruitable stroke work. Overall, this study shows that cardiovascular collapse characterized by hypotension, myocardial depression, and low systemic vascular resistance occurs after CLP in wild-type mice. However, β2M/αAsGM1 mice exhibit improved hemodynamics and cardiac contractile function after CLP that may account, in part, for our previously observed survival benefit.

Differential effect of imipenem treatment on injury caused by cecal ligation and puncture in wild-type and NK cell-deficient β2-microgloblin knockout mice

2006 ◽  
Vol 290 (2) ◽  
pp. G277-G284 ◽  
Author(s):  
Victor T. Enoh ◽  
Cheng Y. Lin ◽  
Tushar K. Varma ◽  
Edward R. Sherwood
Keyword(s):  
Metabolic Acidosis ◽  
Knockout Mice ◽  
Nk Cell ◽  
Plasma Concentrations ◽  
Cecal Ligation ◽  
Systemic Infection ◽  
Cecal Ligation And Puncture ◽  
Wild Type ◽  
Term Survival ◽  
The Impact

Our previous studies showed that β2-microglobulin knockout mice treated with anti-asialoGM1 (β2MKO/αAsGM1 mice) are resistant to injury caused by cecal ligation and puncture (CLP). However, CLP-induced injury is complex. Potential mechanisms of injury include systemic infection, cecal ischemia, and translocation of bacterial toxins such as endotoxin and superantigens. Currently, it is unclear which of these mechanisms of injury contributes to mortality in wild-type mice and whether β2MKO/αAsGM1 mice are resistant to any particular mechanisms of injury. In the present study, we hypothesized that systemic infection is the major cause of injury after CLP in wild-type mice and that β2MKO/αAsGM1 mice are resistant to infection-induced injury. To test this hypothesis, wild-type and β2MKO/αAsGM1 mice were treated with the broad-spectrum antibiotic imipenem immediately after CLP to decrease the impact of systemic infection in our model. Treatment of wild-type and β2MKO/αAsGM1 mice with imipenem decreased bacterial counts by at least two orders of magnitude. However, all wild-type mice, whether treated with saline or imipenem, died by 42 h after CLP and had significant hypothermia, metabolic acidosis, and high plasma concentrations of the cytokines interleukin-6, macrophage inflammatory protein-2, and keratinocyte-derived chemokine. β2MKO/αAsGM1 mice showed 40% long-term survival, which was increased to 90% by imipenem treatment. β2MKO/αAsGM1 mice had less hypothermia, decreased metabolic acidosis, and lower cytokine concentrations at 18 h after CLP compared with wild-type mice. These results suggest that infection is not the major cause of mortality for wild-type mice in our model of CLP. Other mechanisms of injury such as cecal ischemia or translocation of microbial toxins may be more important. β2MKO/αAsGM1 mice appear resistant to these early, non-infection-related causes of CLP-induced injury but showed delayed mortality associated with bacterial dissemination, which was ablated by treatment with imipenem.

Transient Receptor Potential Melastatin 2 Protects Mice against Polymicrobial Sepsis by Enhancing Bacterial Clearance

2014 ◽  
Vol 121 (2) ◽  
pp. 336-351 ◽  
Author(s):  
XiaoWei Qian ◽  
Tomohiro Numata ◽  
Kai Zhang ◽  
CaiXia Li ◽  
JinChao Hou ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Knockout Mice ◽  
Transient Receptor Potential ◽  
Cecal Ligation ◽  
Polymicrobial Sepsis ◽  
Bacterial Clearance ◽  
Cecal Ligation And Puncture ◽  
Bacterial Burden ◽  
Wild Type ◽  
Transient Receptor Potential Melastatin

Abstract Background: Recent studies suggest that the transient receptor potential melastatin 2 (TRPM2) channel plays an important role in inflammation and immune response. However, the role and mechanism of TRPM2 in polymicrobial sepsis remain unclear. Methods: The authors explored the effects of genetic disruption of TRPM2 on mortality (n = 15), bacterial clearance (n = 6), organ injury, and systemic inflammation during cecal ligation and puncture–induced sepsis. Electrophysiology, immunoblot, bacterial clearance experiment, and quantitative real-time polymerase chain reaction were used to explore the role and mechanism of TRPM2 in sepsis. Results: After cecal ligation and puncture, Trpm2-knockout mice had increased mortality compared with wild-type mice (73.3 vs. 40%, P = 0.0289). The increased mortality was associated with increased bacterial burden, organ injury, and systemic inflammation. TRPM2-mediated Ca2+ influx plays an important role in lipopolysaccharide or cecal ligation and puncture–induced heme oxygenase-1 (HO-1) expression in macrophage. HO-1 up-regulation decreased bacterial burden both in wild-type bone marrow–derived macrophages and in cecal ligation and puncture–induced septic wild-type mice. Disruption of TRPM2 decreased HO-1 expression and increased bacterial burden in bone marrow–derived macrophages. Pretreatment of Trpm2-knockout bone marrow–derived macrophages with HO-1 inducer markedly increased HO-1 expression and decreased bacterial burden. Pretreatment of Trpm2-knockout mice with HO-1 inducer reversed the susceptibility of Trpm2-knockout mice to sepsis by enhancing the bacterial clearance. In addition, septic patients with lower monocytic TRPM2 and HO-1 messenger RNA levels had a worse outcome compared with septic patients with normal monocytic TRPM2 and HO-1 messenger RNA levels. TRPM2 levels correlated with HO-1 levels in septic patients (r = 0.675, P = 0.001). Conclusion: The study data demonstrate a protective role of TRPM2 in controlling bacterial clearance during polymicrobial sepsis possibly by regulating HO-1 expression.

Differential effect of imipenem treatment on wild-type and NK cell-deficient CD8 knockout mice during acute intra-abdominal injury

2006 ◽  
Vol 290 (3) ◽  
pp. R685-R693 ◽  
Author(s):  
Victor T. Enoh ◽  
Chad D. Fairchild ◽  
Cheng Y. Lin ◽  
Tushar K. Varma ◽  
Edward R. Sherwood
Keyword(s):  
Metabolic Acidosis ◽  
Knockout Mice ◽  
Nk Cell ◽  
Cecal Ligation ◽  
High Plasma ◽  
Wild Type ◽  
Term Survival ◽  
Bacterial Counts ◽  
Cecal Wall ◽  
Bacterial Dissemination

CD8 knockout mice depleted of natural killer (NK) cells by treatment with anti-asialoGM1 (CD8KO/αAsGM1 mice) are resistant to injury caused by cecal ligation and puncture (CLP). However, CLP-induced injury is complex. Potential sources of injury include bacterial dissemination, cecal ischemia, and translocation of bacterial toxins. We treated wild-type and CD8KO/αAsGM1 mice with imipenem after CLP to decrease bacterial dissemination. Additional mice were subjected to cecal ligation without puncture of the cecal wall or cecal ligation and removal of cecal contents. Imipenem treatment decreased bacterial counts by at least two orders of magnitude. However, all wild-type mice, whether treated with saline or imipenem, died by 42 h after CLP and exhibited significant hypothermia, metabolic acidosis, and high plasma cytokine concentrations. Wild-type mice subjected to cecal ligation without puncture also died, despite very low bacterial counts in blood, but wild-type mice subjected to cecal ligation and washout of cecal contents survived. In CD8KO/αAsGM1 mice subjected to CLP, imipenem treatment increased survival from 50% to 100%. After cecal ligation without puncture, long-term survival was 80–90% in CD8KO/αAsGM1 mice. Hypothermia, metabolic acidosis, and cytokine production were attenuated in CD8KO/αAsGM1 mice compared with wild-type controls. These results indicate that bacterial dissemination is not a major source of injury in wild-type mice after CLP, but the presence of gut flora in the cecal lumen is required for induction of systemic inflammation after cecal injury. CD8KO/αAsGM1 mice are resistant to the systemic manifestations of cecal injury.

P717Glucagon-like peptide 1 (GLP-1) improves endothelial dysfunction and vascular inflammation in polymicrobial sepsis induced by cecal ligation and puncture (CLP)

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Steven ◽  
J Helmstaedter ◽  
F Pawelke ◽  
K Filippou ◽  
K Frenies ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Clinical Trials ◽  
Endothelial Dysfunction ◽  
Knockout Mice ◽  
Vascular Inflammation ◽  
Cecal Ligation ◽  
Cecal Ligation And Puncture ◽  
Glucose Levels ◽  
Dpp4 Inhibitor ◽  
Cardioprotective Effects

Abstract Objective Sepsis causes severe hypotension, accompanied by high mortality in the setting of septic shock. LEADER, SUSTAIN-6 and other clinical trials revealed cardioprotective and anti-inflammatory properties of GLP-1 analogs like Liraglutide (Lira). We already demonstrated improved survival by amelioration of disseminated intravasal coagulation (DIC) in lipopolysaccharide (LPS)-induced endotoxemia by inhibition of the GLP-1 degrading enzyme dipeptidylpeptidase-4 (DPP-4). With the present study we aim to investigate the mechanism of protective effects of the GLP-1 analog Lira and the DPP4 inhibitor Linagliptin (Lina) in the clinically relevant sepsis model cecal ligation and puncture (CLP). Methods C57/BL6j and endothelial cell-specific GLP-1 receptor knockout mice (Cdh5crexGLP-1rfl/flmice) were used and sepsis was induced by cecal ligation and puncture (CLP). DPP4 inhibitor (Lina, 5mg/kg/d; 3 days) and GLP-1 analog (Lira, 200μg/kg/d; 3 days) were applied subcutaneously. Aortic vascular function was tested by isometric tension recording. Aorta and heart tissue was used for Western blotting, dot blot and qRT-PCR. Endogenous GLP-1 (7–36 and 9–36) and insulin was determined by ELISA. Blood samples were collected for examination of cell count, oxidative stress and glucose levels. Results Body temperature was increased by CLP and normalized by Lina and Lira. Sham- and Lira- but not Lina-treated septic mice showed low blood glucose levels compared to healthy controls. Acetylcholine-induced (endothelium-dependent) vascular relaxation in aorta was impaired by CLP. This was accompanied by vascular inflammation and elevation of IL-6, iNOS, ICAM-1, and TNF-alpha mRNA levels in aortic tissue. Vascular, cardiac and whole blood oxidative stress were increased by CLP. Furthermore, we detected higher levels of IL-6, 3-nitrotyrosine (3-NT) and 4-hydroxynonenal (4-NHE) in plasma of CLP animals. Lina and Lira reduced oxidative stress and vascular inflammation, which was accompanied by improved endothelial function. In addition, CLP treatment in endothelial specific knockout mice of the GLP-1r strongly induced mortality compared to WT mice, with the effect being strongest in the Lira-treated group. Conclusion The present study demonstrates that Lina (DPP4 inhibitor) and the GLP-1 analog Lira ameliorate sepsis-induced endothelial dysfunction by reduction of vascular inflammation and oxidative stress. Clinical trials like LEADER and SUSTAIN-6 proved that GLP-1 analogs like Lira have cardioprotective effects in T2DM patients. The present study, performed in a clinically relevant model of polymicrobial sepsis, reveals that the known cardioprotective effects of GLP-1 might be translated to other diseases which affect the cardiovascular system like sepsis, underlining the potent anti-inflammatory effects of GLP-1 analogs.

Muscle metabolism and cardiac function of the myopathic hamster following training

1977 ◽  
Vol 43 (6) ◽  
pp. 936-941 ◽  
Author(s):  
W. L. Sembrowich ◽  
M. B. Knudson ◽  
P. D. Gollnick
Keyword(s):  
Skeletal Muscle ◽  
Cardiac Function ◽  
Myocardial Function ◽  
Cardiac Contractility ◽  
Muscle Metabolism ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Treadmill Running ◽  
Succinate Dehydrogenase Activity ◽  
Positive Effect

The effect of 18 wk of treadmill running on skeletal muscle metabolism and myocardial function of normal and myopathic hamsters was examined. BIO 14.6 hamsters could tolerate an exercise intensity of about 18 m/min for 40 min, 5 days/wk. Further increases in speed or number of bouts per day resulted in a falloff in performance. Normal hamsters could tolerate higher speeds and longer exercise bouts. Exercise did not change the severity of lesions of either the heart or skeletal muscle of the myopathic hamsters. A training effect was evidenced by increased succinate dehydrogenase activity in the soleus muscle. Cardiac function was evaluated as contractility measured from left ventricular pressure curves and expressed as (dP/dt)/kP. The results suggested that cardiac contractility was not as severely depressed in the trained BIO 14.6 strain of hamsters as in nontrained controls. However, (dP/dt)/kP was lower in the trained myopathic animals than in normal hamsters. ATP, CP, and glycogen levels were lower in myopathic hamsters with the lowest values occurring in the trained group. These data demonstrate that the BIO 14.6 strain of hamster can tolerate exercise training and that such training may have a positive effect on cardiac function.

scholarly journals Effect of dobutamine on intrinsic myocardial function and myocardial apoptosis in septic rats with myocardial dysfunction

2020 ◽  
Author(s):  
Xiang-Xu Tang ◽  
Ya-Qian Xu ◽  
Xiao-Meng Dai ◽  
Yun Xing ◽  
Duo-Meng Yang ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Myocardial Function ◽  
Myocardial Dysfunction ◽  
Cecal Ligation ◽  
Left Ventricular ◽  
Cardiomyocyte Apoptosis ◽  
Fatty Acid Binding ◽  
Myocardial Apoptosis ◽  
Tnf Α

Abstract Background Dobutamine (DOB) has been recommended as the first-line inotrope for septic patients with low cardiac output, but its long-term impact on intrinsic myocardial dysfunction during sepsis remains unclear. This study investigated the long-term effect of DOB on intrinsic myocardial function and cardiomyocyte apoptosis in sepsis. Methods Male Sprague-Dawley rats were randomly divided into sham and cecal ligation and puncture (CLP) groups. The intrinsic myocardial function and other organ functions were measured at different time points, the inflammatory response and serum biomarkers of myocardial injury were also determined. In separate experiments, the effect of DOB (5 or 10 µg/kg) treatment on survival, intrinsic myocardial function, serum and myocardial cytokines and myocardial apoptosis were measured in septic rats. Results The mortality rate of septic rats was 70% on day 10 after CLP. At 6 h after CLP, the left ventricular ± dP/dt were significantly depressed, serum tumor necrosis factor (TNF) –α level, cardiac TNF-α, intercellular adhesion molecule and vascular cell adhesion molecule-1 (VCAM-1) mRNA, and VCAM-1 protein levels were increased, but not serum cTnI, N-terminal pro-brain natriuretic peptide (NT-proBNP), heart-type fatty acid-binding protein (H-FABP), creatinine and urea nitrogen concentrations as well as lung wet-dry weight ratios in CLP group compared with those in sham group. At 9 h after CLP, serum alanine aminotransferase and aspartate aminotransferase activities were higher in CLP rats than controls. At 6 h after CLP, treatment with DOB did not affect the left ventricular ± dP/dt, the levels of TNF-α, interleukin (IL) − 1β and IL-6 in the serum and myocardium as well as cardiomyocyte apoptosis at 20 h after CLP. However, administration of 10.0 µg/kg DOB at 6 h after CLP significantly increased serum IL-10 level and improved survival in septic rats. Conclusions The intrinsic myocardial depression occurs earlier than hepatic and renal dysfunction in severe sepsis and serum cTnI, NT-proBNP and H-FABP are not suitable as an early biomarker for this kind of cardiac dysfunction. For septic rats, DOB treatment in the presence of intrinsic myocardial dysfunction neither improves myocardial function nor attenuates myocardial inflammation and cardiomyocyte apoptosis at the later stage of sepsis.

One-day cold perfusion of bimakalim and butanedione monoxime restores ex situ cardiac function

1996 ◽  
Vol 271 (5) ◽  
pp. H1884-H1892 ◽  
Author(s):  
D. F. Stowe ◽  
B. M. Graf ◽  
S. Fujita ◽  
G. J. Gross
Keyword(s):  
Cardiac Function ◽  
Myocardial Function ◽  
Left Ventricular Pressure ◽  
Katp Channels ◽  
Left Ventricular ◽  
Ex Situ ◽  
Control Group ◽  
Cardiac Efficiency ◽  
Time Control ◽  
Butanedione Monoxime

Bimakalim (Bim), an opener of ATP-sensitive K+ (KATP) channels, was given alone or with 2,3-butanedione monoxime (BDM), a reversible uncoupler of contractility, to protect myocardial function during 1 day of hypothermia. Left ventricular pressure (LVP), coronary flow (CF), percent O2 extraction (%O2E), and cardiac efficiency were measured in 96 isolated, perfused guinea pig hearts divided into seven groups: 1) cold control (no drugs); 2) BDM; 3) Bim; 4) BDM + Bim; 5) BDM + glibenclamide (Glib, a blocker of KATP channels); 6) BDM + Bim + Glib; and 7) time control (6 h warm perfusion only). Drugs were given before, during, and initially after 22 h of low CF at 3.8 degrees C. At 26 h (cold groups) or 4 h (warm group) LVP (mmHg; means +/- SE) was similar for time control (94 +/- 4) and BDM + Bim (92 +/- 4) groups, lower and equivalent in the BDM (65 +/- 7) and BDM + Bim + Glib (64 +/- 7) groups, but LVP was higher than in the Bim group (46 +/- 3), and lowest in the cold control (30 +/- 8) group. In addition, only in the BDM + Bim group were basal CF, %O2E, and cardiac efficiency returned to values obtained in the time control group. Epinephrine increased LVP to that of the time control (106 +/- 3) group only in the BDM + Bim group (106 +/- 3) after hypothermia, and CF increases with adenosine, 5-hydroxytryptamine, and nitroprusside were similar to that of the time control group only in the BDM + Bim group after hypothermia. All of the effects of Bim were reversed by Glib. These results indicate that Bim, given with BDM, effectively preserves myocardial function and metabolism as well as inotropic and vasodilatory reserve during long-term hypothermic preservation as if the 1-day hypothermic state had not been instituted. Because the beneficial effects of Bim are blocked by Glib, the protective effect of Bim likely results from maintained KATP channel opening. Treatment with exogenous KATP openers may prove useful in preserving cardiac function in the transplanted heart.

scholarly journals Toll-like Receptor 7 Contributes to Inflammation, Organ Injury, and Mortality in Murine Sepsis

2019 ◽  
Vol 131 (1) ◽  
pp. 105-118 ◽  
Author(s):  
Wenling Jian ◽  
Lili Gu ◽  
Brittney Williams ◽  
Yan Feng ◽  
Wei Chao ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Immune Responses ◽  
Knockout Mice ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Innate Immune ◽  
Organ Injury ◽  
Innate Immune Responses ◽  
Toll Like Receptor ◽  
Wild Type

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Sepsis remains a critical illness with high mortality. The authors have recently reported that mouse plasma RNA concentrations are markedly increased during sepsis and closely associated with its severity. Toll-like receptor 7, originally identified as the sensor for single-stranded RNA virus, also mediates host extracellular RNA-induced innate immune responses in vitro and in vivo. Here, the authors hypothesize that innate immune signaling via Toll-like receptor 7 contributes to inflammatory response, organ injury, and mortality during polymicrobial sepsis. Methods Sepsis was created by (1) cecal ligation and puncture or (2) stool slurry peritoneal injection. Wild-type and Toll-like receptor 7 knockout mice, both in C57BL/6J background, were used. The following endpoints were measured: mortality, acute kidney injury biomarkers, plasma and peritoneal cytokines, blood bacterial loading, peritoneal leukocyte counts, and neutrophil phagocytic function. Results The 11-day overall mortality was 81% in wild-type mice and 48% in Toll-like receptor 7 knockout mice after cecal ligation and puncture (N = 27 per group, P = 0.0031). Compared with wild-type septic mice, Toll-like receptor 7 knockout septic mice also had lower sepsis severity, attenuated plasma cytokine storm (wild-type vs. Toll-like receptor 7 knockout, interleukin-6: 43.2 [24.5, 162.7] vs. 4.4 [3.1, 12.0] ng/ml, P = 0.003) and peritoneal inflammation, alleviated acute kidney injury (wild-type vs. Toll-like receptor 7 knockout, neutrophil gelatinase-associated lipocalin: 307 ± 184 vs.139 ± 41-fold, P = 0.0364; kidney injury molecule-1: 40 [16, 49] vs.13 [4, 223]-fold, P = 0.0704), lower bacterial loading, and enhanced leukocyte peritoneal recruitment and phagocytic activities at 24 h. Moreover, stool slurry from wild-type and Toll-like receptor 7 knockout mice resulted in similar level of sepsis severity, peritoneal cytokines, and leukocyte recruitment in wild-type animals after peritoneal injection. Conclusions Toll-like receptor 7 plays an important role in the pathogenesis of polymicrobial sepsis by mediating host innate immune responses and contributes to acute kidney injury and mortality.

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