Distinct effects of systemic infusion of G-CSF vs. IL-6 on lung and liver inflammation and injury in hemorrhagic shock

Abstract

Production of pro-inflammatory cytokines, such as granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) occurs at multiple tissue sites in hemorrhagic shock (HS), resulting in elevated circulating plasma levels. The current study was designed to test the hypothesis that circulating G-CSF and IL-6 contribute to polymorphonuclear neutrophilic granulocyte (PMN)-mediated inflammation and organ injury in HS. Sprague-Dawley rats were subjected to decompensated HS (mean arterial blood pressure = 40 mm Hg for 2.5 h), followed by resuscitation with lactated Ringer's solution with or without G-CSF (3 microg/kg) or IL-6 (3 microg/kg). Animals were killed 4 h after resuscitation, and their lungs and livers were assessed quantitatively for PMN infiltration, organ injury, and activation of NF-kappaB and signal transducer and activator or transcription (STAT) 3. Infusion of G-CSF during resuscitation increased PMN infiltration into the lungs by 2.4-fold (P < 0.01) compared with animals resuscitated with lactated Ringer's solution alone. Increased PMN infiltration was accompanied by interstitial edema and pneumocyte swelling, resulting in a 42% increase in lung alveolar wall cross-sectional surface area (P < 0.01) and a 3.7-fold increase in Stat3 activity (P < 0.01). G-CSF infusion did not affect PMN infiltration into the liver and was accompanied by a 68% decrease in focal hepatocellular necrosis (P < 0.01). Infusion of IL-6, in contrast, dramatically decreased inflammation…