Intravenous immunoglobulin modulates human mononuclear phagocyte tumor necrosis factor-alpha production in vitro.
Mononuclear phagocytes (MO) secrete tumor necrosis factor-alpha (TNF) in response to inflammatory stimuli, most notably the bacterial product lipopolysaccharide (LPS). Cross-linking of MO Fc receptors also induces TNF release. Immunoglobulin for i.v. use is currently being investigated for the treatment and prophylaxis of neonatal sepsis and for the treatment of various syndromes of autoimmune dysfunction in children and adults. We examined the in vitro effect of immunoglobulin-gamma (IgG) on neonatal (cord blood) monocyte and adult MO TNF production. Kinetic studies were performed on MO incubated with IgG alone and on MO preincubated with IgG and stimulated with interferon-gamma/LPS. Incubation of MO in IgG (1-25 g/L) for 2, 6, and 24 h did not stimulate TNF secretion or production. However, enhanced TNF secretion was detected in MO preincubated in IgG and subsequently stimulated with interferon-gamma/LPS. TNF secretion by cord blood monocytes was increasingly enhanced by preincubation for 6 h with 1, 10, and 25 g/L IgG (2413.1 +/- 1389.4, p < 0.05; 4070.4 +/- 3069.2, p < 0.005; and 6383.7 +/- 2982.2, p < 0.005 versus 1215 +/- 575.9 ng/L, respectively, in cells preincubated in medium alone). Significant enhancement was also detected in cord blood monocytes preincubated in IgG for 2 h. TNF secretion by adult MO was similarly enhanced (6082.0 +/- 1732.8, p < 0.05; 7158.8 +/- 3938.2, p < 0.05; and 7302.7 +/- 3451.4, p < 0.05 versus 3353.2 +/- 2946.7 ng/L for 1, 10, and 25 g/L IgG, respectively, versus preincubation in medium alone). In additional experiments performed with Fc, Fab, and F(ab')2 fragments, only F(ab')2 fragments yielded positive results.(ABSTRACT TRUNCATED AT 250 WORDS)
Darville
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Arkansas Children's Hospital, Little Rock 72202-3591.
Tabor
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Simpson
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Jacobs
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D000328:Adult; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology; D007074:Immunoglobulin G / Q000494:pharmacology; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D017452:Receptors, IgG / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000378:metabolism
D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D008070:Lipopolysaccharides; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma