Effect of a human IgG preparation rich in antibodies to a wide range of lipopolysaccharides on gram‐negative bacterial sepsis in burned mice

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Abstract
A human intravenous IgG preparation (Anti-LPS IgG) rich in antibodies to different lipopolysaccharides (LPS) and a normal human intravenous IgG (NIgG) were investigated for their ability to confer passive immunity. Both preparations were given at the time of infection (prophylaxis) or during sepsis (therapy) to burned mice with lethal infection induced by various clinically relevant gram-negative bacteria. When given at the time of infection both IgG preparations (5 mg/mouse) inhibited lethality induced by some bacteria (Pseudomonas aeruginosa serogroup G and B), but not others (Serratia marcescens, Klebsiella pneumonia, Proteus mirabilis), indicating a protection by by strain-specific antibodies. However, no significant protection was seen when mice were treated during sepsis. The range of specific antibody titers to the whole live bacteria and heat-killed (LPS-preserved) bacteria in the NIgG paralleled that of Anti-LPS IgG; however, the magnitude of the antibody titers did not accurately reflect the protective capacity in vivo. Thus, the exact specificity of the protective antibodies is still unknown. The protective effect of both IgG preparations was dose-dependent; at low IgG doses (0.5 mg/mouse) better protection was obtained with Anti-LPS IgG, whilst at higher doses (> or = 1 mg/mouse) both preparations exhibited identical effects. Low doses of either IgG preparation in combination with subtherapeutic doses of piperacillin significantly enhanced early survival (day 2 for NIgG and day 2 + 3 for Anti-LPS IgG) against P. aeruginosa, but the protective effect waned thereafter. We conclude that a strain-specific antibacterial effect in a compromised mouse infection model can be obtained by early passive immunization with human IgG from large plasma pools. It is suggested that Anti-LPS IgG or NIgG may be of benefit in some cases of gram-negative sepsis when administered as prophylaxis together with proper antibiotic treatment.

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