Differences in anti-inflammatory actions of intravenous immunoglobulin between mice and men: more than meets the eye

Intravenous immunoglobulin (IVIg) is a therapeutic preparation of polyspecific human IgGs purified from plasma pooled from thousands of individuals. When administered at a high dose, IVIg inhibits inflammation and has proven efficacy in the treatment of various autoimmune and systemic inflammatory d...

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Main Authors: Angela SW eTjon, Rogier evan Gent, Teunis B eGeijtenbeek, Jaap eKwekkeboom
Format: Article
Language:English
Published: Frontiers Media S.A. 2015-04-01
Series:Frontiers in Immunology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00197/full
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author Angela SW eTjon
Rogier evan Gent
Teunis B eGeijtenbeek
Jaap eKwekkeboom
author_facet Angela SW eTjon
Rogier evan Gent
Teunis B eGeijtenbeek
Jaap eKwekkeboom
author_sort Angela SW eTjon
collection DOAJ
description Intravenous immunoglobulin (IVIg) is a therapeutic preparation of polyspecific human IgGs purified from plasma pooled from thousands of individuals. When administered at a high dose, IVIg inhibits inflammation and has proven efficacy in the treatment of various autoimmune and systemic inflammatory diseases. Importantly, IVIg therapy can ameliorate both auto-antibody-mediated and T-cell mediated immune-pathologies. In the last few decades, extensive research in murine disease models has resulted in the elucidation of two novel anti-inflammatory mechanisms-of-action of IVIg: induction of FcγRIIB expression by sialylated Fc, and stimulation of regulatory T cells. Whereas controversial findings in mice studies have recently inspired intense scientific debate regarding the validity of the sialylated Fc-FcγRIIB model, the most fundamental question is whether these anti-inflammatory mechanisms of IVIg are operational in humans treated with IVIg. In this review, we examine the evidence for the involvement of these anti-inflammatory mechanisms in the therapeutic effects of IVIg in humans. We demonstrate that, although several elements of both immune-modulatory pathways of IVIg are activated in humans, incorrect extrapolations from mice to men have been made on the molecular and cellular components involved in these cascades that warrant for critical re-evaluation of these anti-inflammatory mechanisms of IVIg in humans.
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spelling doaj.art-3d509a4f2b3345bab38abfa59537d91b2022-12-22T03:43:35ZengFrontiers Media S.A.Frontiers in Immunology1664-32242015-04-01610.3389/fimmu.2015.00197137783Differences in anti-inflammatory actions of intravenous immunoglobulin between mice and men: more than meets the eyeAngela SW eTjon0Rogier evan Gent1Teunis B eGeijtenbeek2Jaap eKwekkeboom3Erasmus MC Erasmus MC Academic Medical CenterErasmus MC Intravenous immunoglobulin (IVIg) is a therapeutic preparation of polyspecific human IgGs purified from plasma pooled from thousands of individuals. When administered at a high dose, IVIg inhibits inflammation and has proven efficacy in the treatment of various autoimmune and systemic inflammatory diseases. Importantly, IVIg therapy can ameliorate both auto-antibody-mediated and T-cell mediated immune-pathologies. In the last few decades, extensive research in murine disease models has resulted in the elucidation of two novel anti-inflammatory mechanisms-of-action of IVIg: induction of FcγRIIB expression by sialylated Fc, and stimulation of regulatory T cells. Whereas controversial findings in mice studies have recently inspired intense scientific debate regarding the validity of the sialylated Fc-FcγRIIB model, the most fundamental question is whether these anti-inflammatory mechanisms of IVIg are operational in humans treated with IVIg. In this review, we examine the evidence for the involvement of these anti-inflammatory mechanisms in the therapeutic effects of IVIg in humans. We demonstrate that, although several elements of both immune-modulatory pathways of IVIg are activated in humans, incorrect extrapolations from mice to men have been made on the molecular and cellular components involved in these cascades that warrant for critical re-evaluation of these anti-inflammatory mechanisms of IVIg in humans.http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00197/fullregulatory T cellsIVIgsialylationFcγ receptorsAnti-inflammatory mechanisms
spellingShingle Angela SW eTjon
Rogier evan Gent
Teunis B eGeijtenbeek
Jaap eKwekkeboom
Differences in anti-inflammatory actions of intravenous immunoglobulin between mice and men: more than meets the eye
Frontiers in Immunology
regulatory T cells
IVIg
sialylation
Fcγ receptors
Anti-inflammatory mechanisms
title Differences in anti-inflammatory actions of intravenous immunoglobulin between mice and men: more than meets the eye
title_full Differences in anti-inflammatory actions of intravenous immunoglobulin between mice and men: more than meets the eye
title_fullStr Differences in anti-inflammatory actions of intravenous immunoglobulin between mice and men: more than meets the eye
title_full_unstemmed Differences in anti-inflammatory actions of intravenous immunoglobulin between mice and men: more than meets the eye
title_short Differences in anti-inflammatory actions of intravenous immunoglobulin between mice and men: more than meets the eye
title_sort differences in anti inflammatory actions of intravenous immunoglobulin between mice and men more than meets the eye
topic regulatory T cells
IVIg
sialylation
Fcγ receptors
Anti-inflammatory mechanisms
url http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00197/full
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AT teunisbegeijtenbeek differencesinantiinflammatoryactionsofintravenousimmunoglobulinbetweenmiceandmenmorethanmeetstheeye
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