EFFECT OF AN INTERLEUKIN-1 RECEPTOR ANTAGONIST ON THE HEMODYNAMIC MANIFESTATIONS OF GROUP-B STREPTOCOCCAL SEPSIS

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 a nesthetized, mechanically ventilated piglets that received a continuou s infusion of group B streptococci (GBS) (7.5 x 10(7) colony-forming u nits/kg/min). Systemic (Psa), pulmonary artery (Ppa), and wedge (Pwp) pressures and cardiac output were measured pre-GBS and every 30 min du ring GBS infusion. After 15 min of bacterial infusion the control grou p 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 mu g/kg/min). In comparing IL-1ra-treated animals with controls from t he 15-min GBS baseline to the succeeding septic study period (45-120 m in), the following treatment effects were noted (120-min values shown) : mean Psa remained elevated in treatment compared with control animal s (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 tr eatment 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 dif ferent between groups over time. Median length of survival was signifi cantly longer (p = 0.04) in treated (226 min) compared with control an imals (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 neon ate.