Neutralizing Activity of Human Immunoglobulin Preparation Against Toxic Shock Syndrome Toxin-1

Human intravenous immunoglobulin (IVIG) preparation containing a variety of antibodies is widely used against severe infectious diseases. Although IVIG is supposed to promote phagocytosis of opsonized bacteria and neutralize several bacterial toxins, it is unclear what antibodies are responsible for the effect in clinical use. In this study, we found that IVIG showed neutralizing activity against toxic shock syndrome toxin-1 TSST-1, produced by methicillin-resistant Staphylococcus aureus (MRSA) Whereas intravenous inoculation with culture medium of MRSA 1945 strain into ICR mice causes immediate death, all of the mice survived in case of previous administraation of IVIG. Such effect might be attributed to neutralization of TSST-1. Murine splenocytes incubated with TSST-1 (1.0ng/mL) for 48 hours produced IFN-γ. By addition of IVIG at 100μg/mL into culture medium, production of IFN-y was completely inhibited. From IVIG, anti-TSST-1 antibody was purified by affinity chromatography as one of the effective antibodies. MRSA 1945 mixed with dextran-based microcarrier beads and injected subcutaneously into mice resulted in the formation of abscess and excretion of TSST-1 in serum for 14 days. IVIG and anti-TSST-1 antibody neutralized TSST-1 in blood 24 hours after infection, although bacterial count was kept constant. Experimental rabbit TSS model was established by synergism with lipopolysaccharide (LPS) of Escherichia coli. Anti-TSST-1 antibody protected NZW rabbits from lethal challenge with TSST-1 (1μg/kg, i.v.) 4 hours before LPS in a dosedependent manner (10μg/kg, i.v.), whereas all of the NZW rabbits died in the control group. Thus, IVIG may be a useful tool in the prevention and perhaps therapy of staphylococcal infections and TSS.