title: Acute removal of common sepsis mediators does not explain the effects of extracorporeal blood purification in experimental sepsis.
abstract: The effect of extracorporeal blood purification on clinical outcomes in sepsis is assumed to be related to modulation of plasma cytokine concentrations. To test this hypothesis directly, we treated rats that had a cecal ligation followed by puncture (a standard model of sepsis) with a modest dose of extracorporeal blood purification that did not result in acute changes in a panel of common cytokines associated with inflammation (TNF-α, IL-1β, IL-6, and IL-10). Pre- and immediate post-treatment levels of these cytokines were unchanged compared to the sham therapy of extracorporeal circulation without blood purifying sorbent. The overall survival to 7 days, however, was significantly better in animals that received extracorporeal blood purification compared to those with a sham procedure. This panel of common plasma cytokines along with alanine aminotransferase and creatinine was significantly lower 72 h following extracorporeal blood purification compared to sham-treated rats. Thus, the effects of this procedure on organ function and survival do not appear to be due solely to immediate changes in the usual measured circulating cytokines. These results may have important implications for the design and conduct of future trials in sepsis including defining alternative targets for extracorporeal blood purification and other therapies.
authors.affiliation: The CRISMA (Clinical Research, Investigation, and Systems Modeling of Acute illness) Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Peng
authors.forename: Hong-Zhi
authors.initials: HZ
authors.lastname: Wang
authors.forename: Melinda J
authors.initials: MJ
authors.lastname: Carter
authors.forename: Morgan V
authors.initials: MV
authors.lastname: Dileo
authors.forename: Jeffery V
authors.initials: JV
authors.lastname: Bishop
authors.forename: Fei-Hu
authors.initials: FH
authors.lastname: Zhou
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Wen
authors.forename: Thomas
authors.initials: T
authors.lastname: Rimmelé
authors.forename: Kai
authors.initials: K
authors.lastname: Singbartl
authors.forename: William J
authors.initials: WJ
authors.lastname: Federspiel
authors.forename: Gilles
authors.initials: G
authors.lastname: Clermont
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D003404:Creatinine / Q000097:blood; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D024243:HMGB1 Protein / Q000097:blood; D006440:Hemofiltration; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000097:blood* / Q000628:therapy*; D018709:Statistics, Nonparametric; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016207:Cytokines; D024243:HMGB1 Protein; D007375:Interleukin-1; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D003404:Creatinine; D000410:Alanine Transaminase