SummaryStudies have shown that human neonates who develop group B streptococcal sepsis usually lack opsonic antibody (Ab) to their infecting strain and that these neonates may also have impaired polymorphonuclear leukocyte (PMN) function. The present study was designed to determine the efficacy of administration of PMNs or opsonic Ab-contPining serum in protecting against group B streptococcal infection in a newborn rat model. After intraperitw neal (IP) injection of -5 x 106 streptococci, animals received separate IP injections of saline, serum lacking opsonic antibody (Ab negative), Ab positive serum or washed adult human PMNs (2 x 106). The mortality rate in 55 neonatal rats infected with group B streptococci who received saline or Ab negative serum was 91%. In contrast, 40 animals who received adult human PMNs at the time of inoculation had a survival rate of ! N% (P < 0.001).Human serum containing opsonic antibody also provided significant protection against mortality in this model (survival rate 51%, P < 0.001). Leukocvtes from normal term neonates. stressedbemates, or ones pietreated with cytochalasin B offered less protection than did functional adult human cell (P < 0.001).
SpeculationThis study provides evidence for polymorphonuclear leukocyte (PMN) dysfunction as another risk factor in group B streptococcal disease and suggests that fully functional PMNs are required for protection. Furthermore, this model involving the administration of human PMNs to an animal appears to have the potential for the in viw evaluation of PMN function in neonates and other compromised hosts. (2) have demonstrated the absolute requirement of specific antibody for significant opsonization of group B streptococci. In previous studies, we have shown that human neonates who develop group B streptococcal sepsis usually lack opsonic antibody to their infecting strains (10) and that these neonates may also have impaired polymorphonuclear leukocyte function (19). Inasmuch as opsonization and phagocytosis represent the most important host defense mechanisms in clearing the body of these bacteria, the present study was designed to determine the effects of passively supplying functional human polymorphonuclear leukocytes (PMNs) or serum containing opsonic antibody in protecting against group B streptococcal infection in a newborn rat model.
METHODS PREPARATION OF ORGANISMSGroup B streptococci type I11 were isolated from the blood and cerebrospinal fluid of infected infants. The strains were cultured at 37°C in Todd-Hewitt broth (Difco Laboratories, Detroit, MI), washed and concentrated in phosphate-buffered saline by centrifugation to contain 5.0 X 10' to 1.0 X lo9 colony-forming units per ml, as previously described (10, 17).
NEONATAL RAT INFECTIONSSprague-Dawley outbred pregnant female rats (Holtzman) were obtained one wk before delivery. When tested, maternal rat serum did not appear to contain signif~cant opsonic activity against most of the strains we used. The neonatal progeny less than 24 hr-old were randomly assigned to gro...