TY - JOUR
T1 - Essential role for IL-6 in postresuscitation inflammation in hemorrhagic shock
AU - Meng, Zhi Hong
AU - Dyer, Kevin
AU - Billiar, Timothy R.
AU - Tweardy, David J.
PY - 2001
Y1 - 2001
N2 - 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-κB 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.
AB - 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-κB 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.
KW - Alveolar wall cross-sectional surface area
KW - Focal liver necrosis
KW - Interleukin-6
KW - Myeloperoxidase
KW - Neutrophils
KW - Nuclear factor-κB
KW - Signal transducers and activators of transcription proteins
UR - http://www.scopus.com/inward/record.url?scp=17744377966&partnerID=8YFLogxK
U2 - 10.1152/ajpcell.2001.280.2.c343
DO - 10.1152/ajpcell.2001.280.2.c343
M3 - Article
C2 - 11208530
AN - SCOPUS:17744377966
SN - 0363-6143
VL - 280
SP - C343-C351
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
IS - 2 49-2
ER -