title: Adsorption of inflammatory cytokines using a heparin-coated extracorporeal circuit.
abstract: Cardiopulmonary bypass (CPB) surgeries cause an increase in plasma inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) along with whole-body inflammatory responses. The inflammatory responses during a CPB treatment are reduced when using a heparin-coated extracorporeal circuit. Because many cytokines, growth factors, and complements are known to interact with heparin, the reduction of inflammatory responses by a heparin-coated circuit is likely to depend on this heparin-binding nature of the inflammatory cytokines. In this study, the inflammatory cytokines, TNF-alpha and IL-6, in fetal bovine serum (FBS) bound to a heparin-agarose beads (heparin beads)-column and the adsorptions were competitively inhibited on addition of heparin in a concentration-dependent manner. TNF-alpha in FBS required a higher concentration of heparin (50% concentration inhibition [IC50] > 20microg/ml) to inhibit adsorption to the heparin beads-column compared with IL-6, probably because of a stronger interaction between TNF-alpha and heparin-beads. TNF-alpha and IL-6 concentrations in human heparinized blood significantly increased after a CPB treatment. Although the adsorbed amount of IL-6 onto the heparin-coated circuit was low (less than 6% of free circulating IL-6), a significant amount of TNF-alpha adsorbed onto the circuit (23.9-755% of free circulating TNF-alpha). Therefore, the adsorption of inflammatory cytokines, especially TNF-alpha, onto the inner heparin-coated surface of an extracorporeal circuit may partly account for a reduction in inflammatory responses.
authors.affiliation: Department of Surgery II, National Defense Medical College, Tokorzawa, Saitama, Japan. BXB01424@nifty.ne.jp
authors.forename: Masanori
authors.initials: M
authors.lastname: Fujita
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ishihara
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Ono
authors.forename: Hidemi
authors.initials: H
authors.lastname: Hattori
authors.forename: Akira
authors.initials: A
authors.lastname: Kurita
authors.forename: Masafumi
authors.initials: M
authors.lastname: Shimizu
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Mitsumaru
authors.forename: Daisuke
authors.initials: D
authors.lastname: Segawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hinokiyama
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Kusama
authors.forename: Makoto
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Maehara
mesh_terms: D000327:Adsorption; D000368:Aged; D000818:Animals; D002315:Cardiopulmonary Bypass / Q000295:instrumentation; D002417:Cattle; D020099:Coated Materials, Biocompatible; D006493:Heparin; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D020099:Coated Materials, Biocompatible; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D006493:Heparin