TITLE: Prevention of Trauma/Hemorrhagic Shock-Induced Mortality, Apoptosis, Inflammation and Mitochondrial Dysfunction Using IL-6 as a Resuscitation Adjuvant PRINCIPAL INVESTIGATOR:

Introduction: Previous studies have been conflicting with regards to the effects of peripheral leukocyte apoptosis on clinical outcomes in hemorrhagic and septic shock. No studies have examined the correlation between peripheral blood PMN apoptosis and outcomes in trauma patients following resuscitation from hemorrhagic shock in vivo. Methods: Pre-operative, post-operative, and 24-hour venous samples were drawn from 31 trauma patients requiring emergent laparotomy or thoracotomy. All patients were in hemorrhagic shock and were resuscitated intra-operatively. Leukocyte apoptosis was measured pre-operatively, post-operatively and at 24 hours via nucleosome ELISA and TUNEL staining, and patient records were examined for 30-day mortality, organ failure and infection rates. Results: Subjects who survived to hospital discharge without developing any infections had significantly higher post-operative nucleosome levels compared to those who did develop an infection (49.8 mU/mg versus 19.8 mU/mg, p=0.02). This trend persisted when analyzing by specific type of infection. TUNEL staining revealed that 72% of apoptotic cells were PMNs. There were no statistically significant correlations between nucleosome levels and survival. Conclusions: In patients with hemorrhagic shock, increased peripheral blood PMN apoptosis is associated with reduced risk of developing subsequent infection. Previous research has shown that high levels of apoptosis in circulating neutrophils following shock may have a protective effect by preventing neutrophil infiltration and limiting release of harmful oxygen radicals in the tissues. Thus, neutrophil apoptosis may render tissues less susceptible to injury and subsequent infection consistent with strategies aimed at benefiting this patient population by limiting PMN number and aberrant function early in the resuscitation period.