Essential role for IL-6 in postresuscitation inflammation in hemorrhagic shock.
Interleukin-6 (IL-6) is produced within multiple tissues and can be readily detected in the circulation in resuscitated hemorrhagic shock (HS). Instillation of IL-6 into lungs of normal rats induces polymorphonuclear neutrophilic granulocyte (PMN) infiltration and lung damage, while infusion of IL-6 into the systemic circulation of rats during resuscitation from HS reduces PMN recruitment and lung injury. The current study was designed to determine whether or not IL-6 makes an essential contribution to postresuscitation inflammation and which of the two effects of IL-6, its local proinflammatory effect or its systemic anti-inflammatory effect, is dominant in HS. Wild-type and IL-6-deficient mice were subjected to HS followed by resuscitation and death 4 h later. IL-6-deficient mice subjected to HS did not demonstrate any features of postresuscitation inflammation observed in wild-type mice, including increased PMN infiltration into the lungs, increased alveolar cross-sectional surface area, increased PMN infiltration into the liver, increased liver necrosis, increased signal transducer and activator of transcription 3 activation, and increased nuclear factor-kappaB activity. These findings indicate that IL-6 is an essential component of the postresuscitation inflammatory cascade in HS and that the local proinflammatory effects of IL-6 on PMN infiltration and organ damage in HS dominate over the anti-inflammatory effects of systemic IL-6.
Meng
Z H
ZH
Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
Dyer
K
K
Billiar
T R
TR
Tweardy
D J
DJ
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology*; D015850:Interleukin-6 / Q000172:deficiency / Q000502:physiology*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009336:Necrosis; D009504:Neutrophils / Q000378:metabolism*; D012151:Resuscitation; D050796:STAT3 Transcription Factor; D012771:Shock, Hemorrhagic / Q000378:metabolism / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; D015850:Interleukin-6; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators