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 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.
Vallette
J D
JD
Department of Pediatrics, University of Miami School of Medicine, Florida 33101, USA.
Goldberg
R N
RN
Suguihara
C
C
Del Moral
T
T
Martinez
O
O
Lin
J
J
Thompson
R C
RC
Bancalari
E
E
D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy* / Q000503:physiopathology; D012795:Sialoglycoproteins / Q000627:therapeutic use*; D013290:Streptococcal Infections / Q000188:drug therapy* / Q000503:physiopathology; D013292:Streptococcus agalactiae / Q000302:isolation & purification; D013552:Swine
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins