Requirements for NF-kappaB activation in hemorrhagic shock.
The activation of nuclear factor (NF)-kappaB contributes to the dysfunctional inflammatory response accompanying resuscitation from hemorrhagic shock (HS), in part through induction of pro-inflammatory cytokines including granulocyte colony-stimulating factor (G-CSF) and interleukin (IL)-6. In previous studies, we demonstrated that G-CSF and IL-6 up-regulation required both the ischemic and resuscitation phases of HS. In this study, we examined whether or not both phases of HS were required for NF-kappaB activation and the kinetics of its activation. Sprague-Dawley rats were subjected to unresuscitated HS with increasing duration of the ischemic phase [compensated HS, 0% shed blood return (SBR); decompensated HS, 35% SBR; and irreversible HS, 70% SBR) or HS (compensated or decompensated)] followed by resuscitation. NF-kappaB activity did not increase in any of the unresuscitated groups compared with sham controls. In contrast, resuscitation as early as 1 h following HS resulted in increased NF-kappaB activity compared with both the unresuscitated shock group and sham controls; NF-kappaB activation persisted for 8 h. Thus, NF-kappaB activation requires both phases of HS, occurs rapidly following resuscitation, and persists throughout the early stages of dysfunctional inflammation following resuscitation.
Hierholzer
Christian
C
Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Germany.
Billiar
Timothy R
TR
Tweardy
David J
DJ
D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000032:analysis / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism*; D009687:Nuclear Proteins / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012151:Resuscitation / Q000379:methods*; D012680:Sensitivity and Specificity; D012771:Shock, Hemorrhagic / Q000378:metabolism* / Q000628:therapy*
D015415:Biomarkers; D018836:Inflammation Mediators; D016328:NF-kappa B; D009687:Nuclear Proteins