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

Abstract

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-c ( IFN-c), soluble IL-2 receptor (sIL-2R) and monokines such as IL-1b, IL-6, IFN-a and tumour necrosis factor (TNF-a) 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.

Use of a five-agent GVHD prevention regimen in recipients of unrelated donor marrow

“…16 Larger studies have not been carried out with this agent. In view of studies by Nachbaur et al 19,20 on the in vitro immuno-modulatory activity of immunoglobulins it appears likely that this might be the mechanism by which an anti GVHD effect can be achieved. Using Pentaglobin the authors demonstrated that proliferation in the mixed-lymphocyte reaction was highly suppressed by IgMcontaining Pentaglobin fractions.…”

“…Cytokine analysis and culture supernatants provide evidence that Pentaglobin leads to a down regulation of interleukin-2, interferon-␥, and monocyte-derived tumornecrosis factor ␣, as well as interleukin-6 release. 19,20 In summary, five-agent GVHD prophylaxis with cyclosporine, methotrexate, anti-thymocyte-globulin, Pentaglobin and metronidazol is an effective regimen. Whether all five components are essential for this effect cannot be stated with certainty.…”

“…[16][17][18] Recent studies have shown that IgM-containing immunoglobulin fractions have a significantly higher modulatory effect on lymphocyte proliferation and cytokine release during alloimmune response in vitro than do IgG-enriched preparations. 19,20 We describe the effect of these five drugs on occurrence of acute and chronic GVHD and survival in recipients of allogeneic blood and marrow transplantation.…”

Suppression of PAMPs, Pathogen-Associated Microbial Patterns, Induced Cytokine Synthesis of PBMC, Human Blood Mononuclear Cells, by Immunoglobulin Preparation

“…There are several reports of the effects of IVIg on cytokine production by human PBMCs. With respect to cytokine production induced by a mixed lymphocyte reaction (MLR), the productions of interleukin (IL)-2, interferon (IFN)-, TNF-, and IL-6 were inhibited by IVIg [21], and the inhibitory action of IVIg on IL-2 production was stronger than that of F(ab') 2 [22]. With respect to cytokine production induced by LPS, the production of IL-6, TNF-, and IL-8 was inhibited [18,23,24], supporting the results shown in this study.…”

Varying Effects of Intravenous Immunoglobulin on Mononuclear Cell Proliferation In Vitro

“…Other studies have shown that high IVIG concentrations inhibit lymphocyte proliferation in the presence of various stimulants irrespective of the cell types including several malignant cell lines (16), and of the IVIG preparations (whole IgG, F(ab′ )2 fragment (17,20), Fc fragments (15,20), or repurified IVIG (17), IgG from single or five donors (17)). …”