Effect of an Interleukin-1 Receptor Antagonist on the Hemodynamic Manifestations of Group B Streptococcal Sepsis

Abstract

IL-1 is purported to be a proximal mediator in the cascade leading to septic shock. To characterize its hemodynamic effects and to ascertain whether its blockade would ameliorate the deleterious consequences of sepsis, an IL-1 receptor antagonist (IL-1ra) was administered to 16 anesthetized, mechanically ventilated piglets that received a continuous infusion of group B streptococci (GBS) (7.5 x 10(7) colony-forming units/kg/min). Systemic (Psa), pulmonary artery (Ppa), and wedge (Pwp) pressures and cardiac output were measured pre-GBS and every 30 min during GBS infusion. After 15 min of bacterial infusion the control group received normal saline, whereas the treatment group received a bolus of IL-1ra (40 mg/kg) followed by a continuous infusion of IL-1ra (60 micrograms/kg/min). In comparing IL-1ra-treated animals with controls from the 15-min GBS baseline to the succeeding septic study period (45-120 min), the following treatment effects were noted (120-min values shown): mean Psa remained elevated in treatment compared with control animals (12.7 +/- 2.5 versus 9 +/- 3.5 kPa; p < 0.001) as did CO (0.21 +/- 0.07 versus 0.13 +/- 0.08 L/min/kg; p < 0.001). Pwp decreased in the treatment compared to the control group over the study period (1 +/- 0.3 versus 1.6 +/- 0.7 kPa; p < 0.02). Mean Ppa and mean Pra were not different between groups over time. Median length of survival was significantly longer (p = 0.04) in treated (226 min) compared with control animals (150 min). These data suggest that IL-1 plays an important role in GBS sepsis and septic shock, and that IL-1ra may in part ameliorate the cardiovascular alterations associated with GBS sepsis in the neonate.