Intravenous immune globulin impairs anti-bacterial defences of a cyclophosphamide-treated host.
Since intravenous immune globulin (i.v.IG) could impair the clearance of autologous IgG-coated erythrocytes by the reticuloendothelial system (RES), we speculated that a patient with leucopenia who died of candida septicaemia following high dose i.v.IG may have had an impairment of his RES function. We therefore studied the ability of intact i.v.IG to impair the clearance of both soluble immune complexes and a relatively avirulent strain of E. coli from the blood of mice made leucopenic with cyclophosphamide. In the presence of leucopenia, 800 micrograms/g i.v.IG prolonged the time to clear 50% of the administered IgG anti-dinitrophenyl immune complex (T1/2) from 2.7 min to 12 min, impaired the clearance of E. coli and lowered the LD50 of the strain five-fold. This impaired clearance of soluble complexes and increased mortality (8/67 versus 37/69, P less than 0.001) following bacterial challenge was present for up to 120 and 60 min, respectively, following the administration of i.v.IG. In contrast, no significant impairment in RES function was noted when 200 micrograms/g i.v.IG was administered to leucopenic mice, or when cyclophosphamide alone was given to mice before challenge with either soluble complexes or bacteria. In addition, no change in LD50 was found when mice were pretreated with 800 micrograms/g i.v.IG alone. These data suggest that high doses of i.v.IG may impair anti-microbial defences of a leucopenic host and thereby convert a relatively avirulent organism into a pathogen.
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Department of Bacterial Diseases, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Siegel
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G
Byrne
W R
WR
Trautmann
M
M
Finbloom
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DS
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D003520:Cyclophosphamide / Q000009:adverse effects*; D004136:Dinitrobenzenes / Q000378:metabolism; D004198:Disease Susceptibility; D004927:Escherichia coli Infections / Q000276:immunology* / Q000401:mortality; D005260:Female; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D016756:Immunoglobulins, Intravenous; D007928:Lethal Dose 50; D007970:Leukopenia / Q000139:chemically induced / Q000276:immunology*; D051379:Mice; D008813:Mice, Inbred ICR
C045618:2,4-dinitrophenyl-IgG; D000936:Antigen-Antibody Complex; D004136:Dinitrobenzenes; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D003520:Cyclophosphamide