High Intravenous Doses of Human Immune Globulin Suppress Neonatal Group B Streptococcal Immunity in Rats

We evaluated the effect of intravenously administered immune globulin (IVIG) on neonatal group B streptococcal (GBS) infection in vivo and in vitro. A suckling rat model was used to compare the impact of penicillin (150 mg/kg) with albumin control, high-dose IVIG (2.7 gm/kg), or low-dose IVIG (0.68 gm/kg) on survival and bacteremia. Three lots of IVIG (two standard and one hyperimmune) with varying titers of GBS type III activity were used. An opsonophagocytic assay was then employed to evaluate in vitro the effect of concentrations of penicillin (none to 2.4 micrograms/ml), IVIG (none to 20 mg/ml), organism-specific (GBS type III-specific) activity (none to 1280(-1], and quantity of organisms (10(4) to 10(6] on the killing of several strains of GBS type III. Low doses of IVIG enhanced suckling rat survival (p less than 0.0025) and bacterial clearance (p less than 0.01). High doses of IVIG did not improve survival and in fact delayed bacterial clearance (p less than 0.05) when compared with low doses. Survival and bacterial clearance increased as the GBS type III activity of the IVIG lot increased. GBS opsonophagocytosis was suppressed at all penicillin concentrations (p less than 0.01) by high levels of IVIG (20 mg/ml). High-dose IVIG suppression of GBS opsonophagocytosis decreased as type III activity of the lot increased. We speculate that high doses of nonspecific IVIG may cause blockade of neutrophil or bacterial receptors necessary for GBS immunity in neonates.