INTERLEUKIN-1 RECEPTOR ANTAGONIST IMPROVES SURVIVAL AND PRESERVES ORGAN ADENOSINE-5'-TRIPHOSPHATE AFTER HEMORRHAGIC-SHOCK

Background. This study was designed to determine the role of interleuk in-1 (IL-1) in hemorrhagic shock death. Methods. Pentobarbital anesthe tized C3H/HeN mice (n = 59) were prepared with a femoral arterial cath eter and were randomized to treatment with an IL-1 receptor antagonist (IL-1ra, 10 mg/kg, n = 29) or an equal volume of phosphate-buffered s aline solution (vehicle, n = 30) by subcutaneous bolus injection at 15 minutes before hemorrhage and again at 120 minutes. Continuous posthe morrhage delivery of IL-1ra or vehicle was performed in each group (1. 5 mg IL-1ra in 30 mul/day) through a subcutaneous osmotic pump. Rapid hemorrhage of 4 ml/100 gm weight was followed by normal saline resusci tation of 12 MV/100 gm 60 minutes later. Results. Survival analysis by Wilcoxon rank sum analysis revealed a significantly improved 5-day su rvival in IL-1ra-treated mice (n = 15, 20%) as compared with vehicle-t reated mice (n = 14, 6%, p < 0.001). To determine a possible mechanism of this survival advantage, the remaining mice in each treatment grou p were killed at 30 minutes to obtain blood and tissue samples from th e heart, liver, and kidney for measurement of adenosine-5'-triphosphat e (ATP). No difference in hematocrit, circulating neutrophils, or leve ls of glucose, lactate, or tumor necrosis factor was identified betwee n groups to explain the improved outcome. IL-1ra prevented hemorrhage- induced ATP depletion observed in vital organs of vehicle-treated mice . Conclusions. The data implicate IL-1 in shock-induced ATP depletion and suggest IL-1ra may improve hemorrhagic shock survival by preventin g ATP depletion in vital organs.