Involvement of ionic interactions in cytokine adsorption of polyethyleneimine-coated polyacrylonitrile and polymethyl me
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ORIGINAL ARTICLE Artificial Kidney / Dialysis
Involvement of ionic interactions in cytokine adsorption of polyethyleneimine‑coated polyacrylonitrile and polymethyl methacrylate membranes in vitro Kazuhiro Moriyama1 · Yu Kato2 · Daisuke Hasegawa2 · Yasuyoshi Kurimoto2 · Takahiro Kawaji2 · Tomoyuki Nakamura2 · Naohide Kuriyama2 · Yasuyo Shimomura2 · Osamu Nishida2 Received: 24 February 2020 / Accepted: 29 April 2020 © The Japanese Society for Artificial Organs 2020
Abstract Polyethyleneimine-coated polyacrylonitrile (AN69ST) and polymethyl methacrylate (PMMA) membranes are effective cytokine-adsorbing hemofilters; however, the cytokine-adsorption mechanism remains elusive. This study investigated the involvement of ionic interactions in cytokine adsorption to a negatively charged AN69ST membrane and neutral-charged PMMA membrane. Experimental hemofiltration was performed for 30 min in a closed-loop circulation system using AN69ST and PMMA hemofilters. Tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 concentrations in the test solutions were measured at baseline and at 10 min and 30 min into hemofiltration. To investigate the involvement of ionic interactions in cytokine adsorption, cytokine clearance (CL) was calculated at 10 min into hemofiltration and with three types of solutions at various pH levels (7.6, 7.2, and 6.8). During AN69ST hemofiltration, the CLs of TNF-α, IL-6, and IL-8 were 38 ± 6 mL/ min, 23 ± 7 mL/min, and 78 ± 3 mL/min, respectively, demonstrating a relationship with their respective isoelectric points. During PMMA hemofiltration, the CL of IL-6 peaked at 31 ± 76 mL/min, with no relationship observed between the CL and isoelectric point. When the pH of the test solution shifted from 7.6 to 6.8, the CLs of TNF-α, IL6, and IL-8 increased in the AN69ST hemofilter; whereas, no such trend was observed in the PMMA hemofilter. These results indicated that Ionic interactions play a role in cytokine adsorption by the AN69ST membrane but not the PMMA membrane and highlight the clinical relevance of this finding, as well as the potential practical applications for further hemofilter design. Keywords AN69ST · Cytokine · Hemofiltration · Ionic interaction · Polymethyl methacrylate
Introduction The definition of sepsis has been updated as life-threatening organ dysfunction caused by a dysregulated host response to infection according to the Third International Consensus Definitions for Sepsis and Septic Shock (SEPSIS-3) [1]. As
* Kazuhiro Moriyama [email protected] 1
Laboratory for Immune Response and Regulatory Medicine, Fujita Health University School of Medicine, 1‑98 Dengakubo, Kutsukake‑cho, Toyoake, Aichi 470‑1192, Japan
Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
2
introduced in the new definition, the main danger associated with sepsis is not injury caused by pathogens but rather the subsequent organ damage caused by an uncontrolled immune response. Specifically, the cytokines that flow into the b
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