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

摘要

These studies will determine if IL-6 merits consideration as a resuscitation adjuvant for use by medics at the time of Hextend administration to soldiers suffering from severe battlefield injuries. We demonstrated that leukocyte apoptosis is not sufficiently robust to use as a biomarker to guide patient selection for IL-6. However, we demonstrated that kidney injury accompanies heart, lung, liver and leukocyte apoptosis in rat T/HS and occurs within 4 hours of resuscitation. Studies are underway to determine if kidney injury biomarkers measured in the urine may be used to guide patient selection and to assess benefit. We identified two proteostasis modulators, Hsp70 and Hsp40, as potential key modulators of liver and lung apoptosis in T/HS that may mediate the beneficial effects of IL-6, which raises the possibility of using clinically available proteostasis modulators to prevent cell apoptosis, if IL-6 proves problematic. Finally, we demonstrated in patients with hemorrhagic shock that increased peripheral blood PMN apoptosis is associated with reduced risk of developing subsequent infection consistent with strategies aimed at benefiting this patient population by limiting PMN number and aberrant function early in the resuscitation period.