Effect of hemofiltration filter adsorption on circulating IL-6 levels in septic rats

Abstract

IntroductionNumerous studies have shown that hemofiltration using porous synthetic membranes can and does remove a wide range of substances that mediate inflammation from the plasma [1][2]. Limited evidence supports the notion that this treatment can also influence circulating plasma concentrations of various mediators [3][4][5] and mounting evidence suggests that these manipulations have important biologic effects [6][7][8]. Despite these advances, there are no randomized clinical trials demonstrating that hemofiltration improves outcome in patients with sepsis. Furthermore, the exact mechanisms responsible for immunomodulation with hemofiltration remain uncertain. Modern hemofiltration filters may adsorb mediator substances as well as permitting them to pass through the membrane. Determining which of these mechanisms is dominant will be essential to advancing the design of materials and methodology suited to this form of therapy. If adsorption is the primary effect, the surface area of the filters must be ANOVA = one-way analysis of variance; AUC = area under the curve; CLP = cecal ligation and puncture; ELISA = enzyme-linked immunosorbent assay; IL = interleukin; SNK = Student-Newman-Keuls; TNF = tumor necrosis factor. AbstractIntroduction Hemofiltration may modulate the inflammatory response in sepsis through a variety of mechanisms. We sought to distinguish clearance from adsorption as the principal mechanism responsible for reducing circulating IL-6 levels with hemofiltration. Materials and methods Nine hours after cecal ligation and puncture in 18 adult male SpragueDawley rats, we divided the rats into three groups (6 animals each) and placed groups 2 and 3 on a hemofiltration circuit connected between the right carotid artery and femoral vein using an AN69 membrane. In the hemofiltration group (group 2), ultrafiltrate was replaced with lactated Ringer's solution; in the recirculation group (group 3), the ultrafiltrate was reinfused into the animal. A sham group (group 1) had an arteriovenous circuit inserted but no hemofiltration. Blood was obtained for measurement of IL-6 and tumor necrosis factor (TNF) at the start of hemofiltration and after 5 and 11 hours of treatment. Results and discussion IL-6 levels increased only in the sham-treated animals (20.4 ± 11.3 at baseline to 62.3 ± 16.8 pg/ml at 11 hours, P = 0.03) (differences between groups 1 and 2, P = 0.015, and groups 1 and 3, P = 0.028). TNF levels were highly variable but not significantly different among the three groups. Conclusion Hemofiltration-associated reductions in circulating IL-6 levels appear to be secondary to adsorption of mediators to the filter membrane. We do not know whether this is due to direct adsorption of IL-6 per se or to the absorption of other mediators with secondary downregulation of IL-6 production or release. In addition, we could not exclude an interaction between adsorption and hemofiltration.

The effects of early high-volume hemofiltration on prolonged cardiac arrest in rats with reperfusion by cardiopulmonary bypass: a randomized controlled animal study

“…A period of time was given as a range of 0–2, 2–4, 4–6, 6–10, and 10–infinity hours in this figure (expressed as gray color gradation). Marks numbering from 1 to 8 displayed referenced reports on IL-6 removal; 1 and 2 are referring to two differing settings of our study ( 1 is for standard volume hemofiltration and 2 is for high-volume hemofiltration); 3 , Laurent et al [ 19 ] and 4 , Nagashima et al [ 20 ], studies on whole-body ischemia/reperfusion injury; 5 , Kellum et al [ 34 ], 6 , Bellomo et al [ 21 ], 7 , Lu et al [ 35 ], and 8 , Rogiers et al [ 33 ], studies on a sepsis animal model. The studies, 1 , 2 , and 5 – 8 , used the same filter of AN69; therefore, SC was set at 0.3 according to our pilot data.…”

“…Kellum et al [ 34 ] reported blood IL-6 levels during the hemofiltration in sepsis. They showed significantly lower blood IL-6 levels (17 pg/mL) in hemofiltration-treated animals than non-treated animals (62 pg/mL) using the cecal ligation and puncture model of rats.…”

Effects of Hemoadsorption with a Novel Adsorbent on Sepsis: In vivo and in vitro Study

“…In an experiment to compare the relative effects of sieving and adsorption on plasma IL-6 following CLP in rats [20], we found that hemoadsorption was the main mechanism of removal. Hemoadsorption is dependent on membrane material and, during hemofiltration, on filtration operating parameters (e.g.…”

Etanercept Clearance during an in vitro Model of Continuous Venovenous Hemofiltration

“…Protein adsorption to all types of artificial membranes is well described, occurring in the first 20 min of blood-membrane interface [14,15,16]. This mode of clearance has previously been documented for other proteins, such as cytokines, in both laboratory and human studies of CVVH in sepsis [17,18,19,20,21]. Although protein adsorption occurs with AN69 and PS membranes, PMMA membranes were designed specifically for protein adsorption to limit β 2 -microglobulin accumulation and to prevent dialysis-related amyloidosis [22].…”