Nonspecific human IgG reduces survival in neonatal rats infected with Escherichia coli.
BACKGROUND
Human intravenous IgG (IVIG) containing specific antibodies protects neonatal rats from septic death. However, IVIG has immunosuppressive properties and clinical trials of IVIG in neonates at risk for sepsis have yielded conflicting results.


OBJECTIVE
This study was designed to test the hypothesis that nonspecific antibodies in IVIG reduce survival in neonatal rats infected with Escherichia coli.


METHODS
Specific antibodies were adsorbed from IVIG with E. coli to produce IVIG/anti-E. coli-. After transthoracic administration of E. coli, survival was determined in neonatal rats injected intraperitoneally with phosphate-buffered saline, IVIG/anti-E. coli- (500 mg/kg) or IVIG containing anti-E. coli antibodies (IVIG/anti-E. coli+). Complement-mediated hemolytic activity of neonatal rat serum was quantified using sensitized sheep erythrocytes.


RESULTS
Compared with placebo, intraperitoneal IVIG/anti-E. coli- reduced neonatal survival after E. coli infection. In contrast, IVIG/anti-E. coli+ protected infected animals. Both IVIG/anti-E. coli- and IVIG/anti-E. coli+ impaired the complement-mediated hemolytic activity of neonatal rat serum.


CONCLUSIONS
IVIG contained (1) nonspecific antibodies that reduced survival in neonatal rats infected with E. coli and (2) protective anti-E. coli antibodies that enhanced survival in neonatal rats infected with E. coli. We speculate that in clinical trials of IVIG to treat or prevent neonatal sepsis, inconsistent results may be caused, in part, by lot-to-lot variations in the ratio of immunosuppressive, nonspecific antibodies to protective, specific antibodies.
Cole
C W
CW
Department of Pediatrics, University of Louisville School of Medicine, Kentucky, USA.
Feldhoff
R C
RC
Goldsmith
L J
LJ
Jung
E
E
Wilson
R A
RA
Lassiter
H A
HA
D000818:Animals; D000831:Animals, Newborn; D000907:Antibodies, Bacterial / Q000633:toxicity; D000918:Antibody Specificity; D003165:Complement System Proteins / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D004927:Escherichia coli Infections / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy; D006461:Hemolysis; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000633:toxicity*; D066298:In Vitro Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
D000907:Antibodies, Bacterial; D016756:Immunoglobulins, Intravenous; D003165:Complement System Proteins