The role of anti-tumor necrosis factor-α and interleukin-10 in protecting murine neonates from Escherichia coli sepsis

Lally, Kevin P.; Cruz, Emmanuel Tadeus S.; Xue, Hasen

doi:10.1053/jpsu.2000.6862

Cited by 18 publications

(12 citation statements)

References 13 publications

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“…The role of IL-10 in regulating immune response continues to be elucidated, but data suggest that IL-10 levels have an influence on outcome from Gram-negative sepsis. Several reports have demonstrated that administration of recombinant IL-10 is protective against Gram-negative septic shock in murine sepsis models (42)(43)(44). Another study in a similar model demonstrated that administration of antibodies to IL-10 was associated with higher mortality (45).…”

Section: Discussionmentioning

confidence: 99%

Bioartificial Kidney Ameliorates Gram-Negative Bacteria-Induced Septic Shock in Uremic Animals

Fissell

Lou

Abrishami

et al. 2003

Journal of the American Society of Nephrology

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Abstract. The bioartificial kidney (BAK) consists of a conventional hemofiltration cartridge in series with a renal tubule assist device (RAD) containing 10 9 porcine renal proximal tubule cells. BAK replaces filtration, transport, and metabolic and endocrinologic activities of a kidney. Previous work in an acutely uremic dog model demonstrated that BAK ameliorated endotoxin (lipopolysaccharide [LPS])-induced hypotension and altered plasma cytokine levels. To further assess the role of BAK in sepsis in acute renal failure, dogs were nephrectomized and 48 h later administered intraperitoneally with 30 ϫ 10 10 bacteria/kg of E. coli. One hour after bacterial administration, animals were placed in a continuous venovenous hemofiltration circuit with either a sham RAD without cells (n ϭ 6) or a RAD with cells (n ϭ 6). BP, cardiac output, heart rate, pulmonary capillary wedge pressure, and systemic vascular resistance were measured throughout the study. All animals tested were in renal failure, with blood urea nitrogen and serum creatinine concentrations greater than 60 and 6 mg/dl, respectively. RAD treatment maintained significantly better cardiovascular performance, as determined by arterial BP (P Ͻ 0.05) and cardiac output (P Ͻ 0.02), for longer periods than sham RAD therapy. Consistently, all sham RAD-treated animals, except one, expired within 2 to 9 h after bacterial administration, whereas all RAD-treated animals survived more than 10 h. Plasma levels of TNF-␣, IL-10, and C-reactive protein (CRP) were measured during cell RAD and sham RAD treatment. IL-10 levels were significantly higher (P Ͻ 0.01) during the entire treatment interval in the RAD animals compared with sham controls. These data demonstrated in a pilot large animal experiment that the BAK with RAD altered plasma cytokine levels in acutely uremic animals with septic shock. This change was associated with improved cardiovascular performance and increased survival time. These results demonstrate that the addition of cell therapy to hemofiltration in an acutely uremic animal model with septic shock ameliorates cardiovascular dysfunction, alters systemic cytokine balance, and improves survival time.

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Section: Discussionmentioning

confidence: 99%

Bioartificial Kidney Ameliorates Gram-Negative Bacteria-Induced Septic Shock in Uremic Animals

Fissell

Lou

Abrishami

et al. 2003

Journal of the American Society of Nephrology

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“…Several reports have demonstrated that administration of recombinant IL-10 is protective against gram-negative septic shock in murine sepsis models [34][35][36]. Another study in a similar model demonstrated that administration of antibodies to IL-10 was associated with higher mortality [37].…”

Section: Discussionmentioning

confidence: 99%

Bioartificial Kidney Alters Cytokine Response and Hemodynamics in Endotoxin-Challenged Uremic Animals

Fissell¹,

Dyke²,

Weitzel³

et al. 2002

Blood Purif

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The mortality from sepsis complicated by renal failure remains extremely high despite the application of modern renal replacement therapy. This study investigated whether treatment with a bioartificial kidney consisting of a hemofilter in a continuous venovenous hemofiltration circuit (CVVH) with a cartridge containing renal proximal tubule cells, also called the Renal Tubule Assist Device (RAD), would alter the course of sepsis in an animal model. The RAD has been previously characterized in vitro and ex vivo and provides transport, metabolic and endocrine activity. Mongrel dogs (n = 10) underwent surgical nephrectomy and 48 h later were treated with CVVH and either a RAD containing cells (n = 5) or an identically prepared sham cartridge (n = 5). After 4 h of therapy, intravenous endotoxin 2 mg/kg was infused over 1 h to simulate gram-negative septic shock. Data on blood pressure, cardiac output and systemic markers of inflammation were collected. Mean peak levels of an anti- inflammatory cytokine, IL-10, were significantly higher in cell-treated animals (15.25 vs. 6.29 ng/ml; p = 0.037), and mean arterial pressures were higher in cell-treated versus sham-treated animals (p < 0.04). We have demonstrated that treatment of an animal model of endotoxin shock and renal failure with a bioartificial kidney has measurable effects on circulating mediators of inflammation and on hemodynamic stability of the challenged animal.

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“…The role of IL-10 in regulating immune response continues to be elucidated, but data suggest that IL-10 levels influence outcome in endotoxin shock and gram-negative sepsis. Several reports have demonstrated that administration of recombinant IL-10 is protective against gram-negative septic shock in murine sepsis models [37–39]. Another study in a similar model demonstrated that administration of antibodies to IL-10 was associated with higher mortality [40].…”

Section: Immunomodulatory Effect Of the Radmentioning

confidence: 99%

The Bioartificial Kidney in the Treatment of Acute Kidney Injury

Song¹,

Humes²

2009

CDT

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Acute kidney injury (AKI) continues to have an exceedingly high mortality rate, despite advances in dialysis technology. Current dialysis therapies replace only the filtration function of the kidney, not the critical transport, metabolic, and endocrine functions of renal tubule cells. Replacement of these additional functions would provide more complete AKI therapy and thereby change the natural history of this disease process. A renal tubule assist device (RAD) containing living renal proximal tubule cells has been successfully engineered and has demonstrated differentiated absorptive, metabolic, and endocrine functions of normal kidney in vitro and ex vivo in animal experiments. The addition of the RAD containing human cells to conventional continuous renal replacement therapy has been shown in preclinical and clinical studies to have the potential to advance AKI treatment, from enhancing renal clearance to providing more complete renal replacement therapy. This “bioartificial kidney” demonstrates metabolic activity with systemic effects and improvement of survival in patients with AKI and multiorgan failure. It also appears to influence systemic leukocyte activation and the balance of inflammatory cytokines, suggesting that cell therapy by use of the RAD may improve morbidity and mortality by altering the proinflammatory state of patients with renal failure. In addition to providing cellular metabolic function, technologies directed toward disrupting systemic inflammatory response may well enhance the clinical outcome of critically ill patients in the future. Innovative approaches to intensive renal care such as the RAD may break the mold of current institutional dialysis therapies and provide numerous opportunities to develop lifesaving technologies.

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The role of anti-tumor necrosis factor-α and interleukin-10 in protecting murine neonates from Escherichia coli sepsis

Cited by 18 publications

References 13 publications

Bioartificial Kidney Ameliorates Gram-Negative Bacteria-Induced Septic Shock in Uremic Animals

Bioartificial Kidney Ameliorates Gram-Negative Bacteria-Induced Septic Shock in Uremic Animals

Bioartificial Kidney Alters Cytokine Response and Hemodynamics in Endotoxin-Challenged Uremic Animals

The Bioartificial Kidney in the Treatment of Acute Kidney Injury

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