Effects of Anti-CD18 Monoclonal Antibody, R15.7, on the Cardiopulmonary Manifestations of Group B Streptococcal Sepsis in Piglets

Abstract

We hypothesized that anti-CD18 monoclonal antibody, R15.7, a murine IgG₁ antibody which blocks leukocyte-endothelial cell adherence, might ameliorate the cardiopulmonary manifestations of sepsis secondary to group B streptococci (GBS). Twenty-six anesthetized, mechanically ventilated newborn piglets received a continuous infusion of GBS (7.5 × 10⁹ cfu/kg/min) and were randomly assigned to a treatment group receiving R15.7 (1 mg/kg i.v.) 15 min prior to GBS infusion or to a control group. Cardiopulmonary measurements, arterial blood gases and peripheral blood leukocytes were obtained over 120 min of R15.7 infusion. GBS infusion caused significant increases in pulmonary artery and systemic arterial blood (Psa) pressures, pulmonary vascular (PVR) and systemic vascular (SVR) resistances, and PVR/SVR ratio with decreases in cardiac output and stroke volume. R15.7-treated piglets maintained significantly higher Psa (p < 0.003), dynamic lung compliance (p < 0.04), PaO₂ and pH (p < 0.05), and lower total lung resistance (p < 0.01) and PaCO₂ (p < 0.04). A longer median survival time was observed in the treatment group (p < 0.01). These data suggest that administration of a CD18-blocking agent prolongs survival in a young animal model of GBS sepsis, possibly secondary to improved tissue perfusion, lung mechanics and acid-base status.