Intravenous immunoglobulin inhibits staphylococcal toxin-induced human mononuclear phagocyte tumor necrosis factor alpha production.
Intravenous gamma immunoglobulin (IVIG) is used as therapy in superantigen-mediated disease, yet its mode of action is not clear. Pooled immunoglobulin G contains high concentrations of staphylococcal exotoxin (SE)-specific antibodies which inhibit the in vitro activation of T cells. However, SE and streptococcal exotoxins are potent stimulators of monocytes as well. Monocytes exposed to SE in vitro release large amounts of tumor necrosis factor alpha (TNF-alpha). The purpose of the present study was to determine if SE-specific antibodies in IVIG can inhibit the activation of monocytes by SE. We examined the in vitro effect of IVIG on the ability of staphylococcal exotoxin A (SEA) and staphylococcal exotoxin B (SEB) to stimulate release of TNF-alpha from human mononuclear phagocytes (MO). Pretreatment of SEA with 0.1 mg of IVIG per ml resulted in a slight decrease of SEA-induced TNF-alpha secretion by MO. In contrast, pretreatment of SEB with 0.1 mg of IVIG per ml resulted in significant (greater than 50%) inhibition of SEB-induced TNF-alpha secretion at 24, 48, 72, and 96 h (P < 0.05 for TNF-alpha levels induced by SEB alone versus SEB pretreated with IVIG at all time points). Enzyme-linked immunosorbent assay and Western immunoblotting assays of the IVIG revealed high concentrations of antibodies against SEB and lower concentrations of antibodies to SEA. These data indicate that IVIG can act in a toxin-specific manner to decrease the MO TNF-alpha response to superantigens. Such inhibition may be one mechanism by which IVIG exerts an immunoregulatory role in superantigen-mediated disease.
Darville
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Department of Pediatric Infectious Diseases, University of Arkansas for Medical Sciences, Little Rock, USA. toni@achasc.uams.edu
Milligan
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Laffoon
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D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D000907:Antibodies, Bacterial / Q000378:metabolism; D001427:Bacterial Toxins / Q000494:pharmacology*; D002448:Cell Adhesion / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005098:Exotoxins / Q000494:pharmacology*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D005098:Exotoxins; D016756:Immunoglobulins, Intravenous; D014409:Tumor Necrosis Factor-alpha