Hemoadsorption removes tumor necrosis factor, interleukin-6, and interleukin-10, reduces nuclear factor-κB DNA binding, and improves short-term survival in lethal endotoxemia*

Kellum, John A.; Song, Mingchen; Venkataraman, Ramesh

doi:10.1097/01.ccm.0000114997.39857.69

Cited by 179 publications

(182 citation statements)

References 20 publications

Supporting

Mentioning

168

Contrasting

Unclassified

Order By: Relevance

“…This technology does not target endotoxin but has been shown to result in rapid in vitro and in vivo elimination of several key cytokines [47]. Recently, 33 septic rats were randomly assigned to receive either hemoadsorption or sham treatment for 3 hours [48].…”

Section: Hemoadsorptionmentioning

confidence: 99%

Clinical review: Blood purification for sepsis

2011

View full text Add to dashboard Cite

Sepsis is the primary cause of death in the intensive care unit. Extracorporeal blood purification therapies have been proposed for patients with sepsis in order to improve outcomes since these therapies can alter the host inflammatory response by non-selective removal of inflammatory mediators or bacterial products or both. Recent technological progress has increased the number of techniques available for blood purification and their performance. In this overview, we report on the latest advances in blood purification for sepsis and how they relate to current concepts of disease, and we review the current evidence for high-volume hemofiltration, cascade hemofiltration, hemoadsorption, coupled plasma filtration adsorption, high-adsorption hemofiltration, and high-cutoff hemofiltration/hemodialysis. Promising results have been reported with all of these blood purification therapies, showing that they are well tolerated, effective in clearing inflammatory mediators or bacterial toxins (or both) from the plasma, and efficacious for improvement of various physiologic outcomes (for example, hemodynamics and oxygenation). However, numerous questions, including the timing, duration, and frequency of these therapies in the clinical setting, remain unanswered. Large multicenter trials evaluating the ability of these therapies to improve clinical outcomes (that is, mortality or organ failure), rather than surrogate markers such as plasma mediator clearance or transient improvement in physiologic variables, are required to define the precise role of blood purification in the management of sepsis.

show abstract

Section: Hemoadsorptionmentioning

confidence: 99%

Clinical review: Blood purification for sepsis

2011

View full text Add to dashboard Cite

show abstract

“…A portion of the septic animal's blood is circulated through an ex vivo circuit including the HA device: a column packed with small adsorptive beads. Key inflammatory cytokines responsible for the propagation of the inflammatory response, including TNF, interleukin(IL)-6, and IL-10, are captured by the device [29]. A calibrated model of cytokine capture was presented by DiLeo et al [31,32] There is preliminary evidence that existing HA devices directly interact with circulating WBCs, the distal effectors of systemic inflammation.…”

Section: Hemoadsorption: a Potential Treatment For Sepsismentioning

confidence: 99%

“…The last two terms capture cytokine adsorption to, and desorption from, the bead bed surface. Adsorption and desorption here represent reversible capture at/near the bead surface, with surface concentration S i defined by Equation (29). The last constant in Equation (29), k bnd , represents irreversible uptake of cytokine into the bead pores .…”

Section: Hemoadsorption Modelmentioning

confidence: 99%

“…Hemoadsorption (HA) is a blood purification treatment that has been shown to improve short term survival in septic rat models, presumably through nonspecific removal of inflammatory mediators [29,30]). A portion of the septic animal's blood is circulated through an ex vivo circuit including the HA device: a column packed with small adsorptive beads.…”

Section: Hemoadsorption: a Potential Treatment For Sepsismentioning

confidence: 99%

“…Parameter identification was performed using the system dynamic model in Equations (28) and (29). The inlet to the first liquid discretization came from the cytokine bath (a continuously-stirred tank), and the liquid outlet of the 20th discretization was returned to the bath; additional experimental details can be found in [56].…”

Section: Hemoadsorption Modelmentioning

confidence: 99%

See 2 more Smart Citations

Modeling and Hemofiltration Treatment of Acute Inflammation

et al. 2016

View full text Add to dashboard Cite

Abstract:The body responds to endotoxins by triggering the acute inflammatory response system to eliminate the threat posed by gram-negative bacteria (endotoxin) and restore health. However, an uncontrolled inflammatory response can lead to tissue damage, organ failure, and ultimately death; this is clinically known as sepsis. Mathematical models of acute inflammatory disease have the potential to guide treatment decisions in critically ill patients. In this work, an 8-state (8-D) differential equation model of the acute inflammatory response system to endotoxin challenge was developed. Endotoxin challenges at 3 and 12 mg/kg were administered to rats, and dynamic cytokine data for interleukin (IL)-6, tumor necrosis factor (TNF), and IL-10 were obtained and used to calibrate the model. Evaluation of competing model structures was performed by analyzing model predictions at 3, 6, and 12 mg/kg endotoxin challenges with respect to experimental data from rats. Subsequently, a model predictive control (MPC) algorithm was synthesized to control a hemoadsorption (HA) device, a blood purification treatment for acute inflammation. A particle filter (PF) algorithm was implemented to estimate the full state vector of the endotoxemic rat based on time series cytokine measurements. Treatment simulations show that: (i) the apparent primary mechanism of HA efficacy is white blood cell (WBC) capture, with cytokine capture a secondary benefit; and (ii) differential

show abstract

IL‐6 adsorption dynamics in hemoadsorption beads studied using confocal laser scanning microscopy

Kimmel¹,

Gibson²,

Watkins³

et al. 2009

J Biomed Mater Res

Self Cite

View full text Add to dashboard Cite

Sepsis is characterized by a systemic inflammatory response caused by infection, and can result in organ failure and death. Removal of inflammatory mediators such as cytokines from the circulating blood is a promising treatment for severe sepsis. We are developing an extracorporeal hemoadsorption device to remove cytokines from the blood using biocompatible, polymer sorbent beads. In this study, we used confocal laser scanning microscopy (CLSM) to directly examine adsorption dynamics of a cytokine (IL-6) within hemoadsorption beads. Fluorescently labeled IL-6 was incubated with sorbent particles, and CLSM was used to quantify spatial adsorption profiles of IL-6 within the sorbent matrix. IL-6 adsorption was limited to the outer 15μm of the sorbent particle over a relevant clinical time period, and intraparticle adsorption dynamics was modeled using classical adsorption/diffusion mechanisms. A single model parameter, α = q max K / D, was estimated by fitting CLSM intensity profiles to our mathematical model, where q max and K are Langmuir adsorption isotherm parameters, and D is the effective diffusion coefficient of IL-6 within the sorbent matrix. Given the large diameter of our sorbent beads (450μm), less than 20% of available sorbent surface area participates in cytokine adsorption. Development of smaller beads may accelerate cytokine adsorption by maximizing available surface area per bead mass.

show abstract

Hemoadsorption removes tumor necrosis factor, interleukin-6, and interleukin-10, reduces nuclear factor-κB DNA binding, and improves short-term survival in lethal endotoxemia*

Abstract: Hemoadsorption was associated with reduced inflammation and improved survival in this murine model of septic shock.

Cited by 179 publications

References 20 publications

Clinical review: Blood purification for sepsis

Clinical review: Blood purification for sepsis

Modeling and Hemofiltration Treatment of Acute Inflammation

IL‐6 adsorption dynamics in hemoadsorption beads studied using confocal laser scanning microscopy

Contact Info

Product

Resources

About