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A comparative study of the in vitro immunomodulatory activity of human intact immunoglobulin (7S IVIG), F(ab′) 2 fragments (5S IVIG) and Fc fragments. Evidence for post‐transcriptional IL‐2 modulation
Author(s) -
NACHBAUR D.,
HEROLD M.,
EIBL B.,
GLASSL H.,
SCHWAIGHOFER H.,
HUBER C.,
GÄCHTER A.,
PICHL M.,
NIEDERWIESER D.
Publication year - 1997
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1997.d01-2148.x
Subject(s) - antibody , peripheral blood mononuclear cell , immunology , cytokine , cytotoxic t cell , receptor , in vitro , tumor necrosis factor alpha , cytotoxicity , biology , autoantibody , microbiology and biotechnology , biochemistry
During the past few decades intravenous immunoglobulin (IVIG) has been used successfully in the treatment of various immunoregulatory disorders. Treatment results have been attributed to immunomodulation mainly via Fc receptors or by anti‐idiotypic antibodies to disease‐causing autoantibodies. From the present study it is clearly evident that 7S IVIG (intact immunoglobulin) as well as 5S IVIG [ F(ab′) 2 fragments] and Fc fragments have a potent immunomodulatory capacity. We demonstrate that mainly 7S IVIG inhibits alloantigen‐induced T‐cell proliferation and generation of cytotoxic T lymphocytes. Reduced interleukin‐2 (IL‐2) protein levels in culture supernatants of IVIG‐supplemented mixed lymphocyte reactions (MLR) but unchanged IL‐2 mRNA levels strongly argue in favour of a post‐transcriptional interference of IVIG with cytokines and/or cytokine production. Interferon‐ γ (IFN‐ γ ), soluble IL‐2 receptor (sIL‐2R) and monokines such as IL‐1 β , IL‐6, IFN‐ α and tumour necrosis factor (TNF‐ α ) were not affected by IVIG supplementation to MLR. Fc fragments were superior to F(ab′) 2 ‐containing IVIG (5S and 7S IVIG) in inhibiting lectin stimulation of peripheral blood mononuclear cells (PBMC), whereas natural killer (NK) cytotoxicity was primarily inhibited by Fc‐bearing IVIG (7S IVIG and Fc fragments), suggesting multiple mechanisms of IVIG immunomodulatory activity.