Am J Physiol Cell Physiol AJP: Gastrointestinal and Liver Physiology
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Am J Physiol Cell Physiol 280: C343-C351, 2001;
0363-6143/01 $5.00
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Vol. 280, Issue 2, C343-C351, February 2001

Essential role for IL-6 in postresuscitation inflammation in hemorrhagic shock

Zhi Hong Meng1, Kevin Dyer2, Timothy R. Billiar3, and David J. Tweardy1

1 Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030; 2 University of Pittsburgh Cancer Institute, Pittsburgh 15213; and 3 Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213

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-kappa B 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.

signal transducers and activators of transcription proteins; nuclear factor-kappa B; neutrophils; myeloperoxidase; alveolar wall cross-sectional surface area; focal liver necrosis; interleukin-6


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