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). Instil lation of IL-6 into lungs of normal rats induces polymorphonuclear neutroph ilic 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 determi ne whether or not IL-6 makes an essential contribution to postresuscitation inflammation and which of the two effects of IL-6, its local proinflammato ry 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 demonstra te any features of postresuscitation inflammation observed in wild-type mic e, including increased PMN infiltration into the lungs, increased alveolar cross-sectional surface area, increased PMN infiltration into the liver, in creased liver necrosis, increased signal transducer and activator of transc ription 3 activation, and increased nuclear factor-kappaB activity. These f indings indicate that IL-6 is an essential component of the postresuscitati on 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-inf lammatory effects of systemic IL-6.