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 POSTTRANSCRIPTIONAL IL-2 MODULATION

During the past few decades intravenous immunoglobulin (IVIG) has been used successfully in the treatment of various immunoregulatory disord ers. Treatment results have been attributed to immunomodulation mainly via Fc receptors or by anti-idiotypic antibodies to disease-causing a utoantibodies. From the present study it is clearly evident that 7S IV IG (intact immunoglobulin) as well as 5S IVIG [F(ab')(2) fragments] an d 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 l ymphocyte reactions (MLR) but unchanged IL-2 mRNA levels strongly argu e in favour of a post-transcriptional interference of IVIG with cytoki nes and/or cytokine production. Interferon-gamma (IFN-gamma), soluble IL-2 receptor (sIL-2R) and monokines such as IL-1 beta, IL-6, IFN-alph a and tumour necrosis factor (TNF-alpha) were not affected by IVIG sup plementation to MLR. Fc fragments were superior to F(ab')(2)-containin g IVIG (5S and 7S IVIG) in inhibiting lectin stimulation of peripheral blood mononuclear cells (PBMC), whereas natural killer (NK) cytotoxic ity was primarily inhibited by Fc-bearing IVIG (7S IVIG and Fc fragmen ts), suggesting multiple mechanisms of IVIG immunomodulatory activity.