Sepsis can result in excessive and maladaptive
inflammation that is responsible for more than 215,00 deaths per year in the United State alone. Current strategies for reducing the morbidity and mortality associated with
sepsis rely on treatment of the syndrome rather than prophylaxis. We have been investigating a modified
tetracycline,
COL-3, which can be given prophylactically to patients at high risk for developing
sepsis. Our group has shown that
COL-3 is very effect at preventing the sequelae of
sepsis if given before or immediately after injury in both rat and porcine
sepsis models. In this study, we wanted to determine the "treatment window" for
COL-3 after injury at which it remains protective.
Sepsis was induced by cecal
ligation and
puncture (CLP). Rats were anesthetized and placed into five groups: CLP (n = 20) = CLP without
COL-3,
sham (n = 5) = surgery without CLP or
COL-3, COL3@6h (n = 10) =
COL-3 given by gavage 6 h after CLP, COL3@12h (n = 10) =
COL-3 given by gavage 12 h after CLP, and COL3@24h (n = 20) =
COL-3 given by gavage 24 h after CLP.
COL-3 that was given at 6 and 12 h after CLP significantly improved survival as compared with the CLP and the CLP@24h groups. Improved survival was associated with a significant improvement in lung pathology assessed morphologically. These data suggest that
COL-3 can be given up to 12 h after
trauma and remain effective.