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Inhibitory Effect of IVIG on IL-17 Production by Th17 Cells is Independent of Anti-IL-17 Antibodies in the Immunoglobulin Preparations

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Abstract

Purpose

Th17 cells and their cytokines play a critical role in the pathogenesis of various autoimmune and inflammatory diseases. Recently, we have demonstrated that intravenous immunoglobulin (IVIG) suppresses differentiation, amplification, and functions of human Th17 cells. In this report we investigated whether IVIG inhibits IL-17 production by Th17 cells cultured in the presence of IL-23 and whether the inhibitory effect of IVIG on IL-17 production implicates anti-IL-17 antibodies.

Methods

Naive CD4+ T cells were stimulated in the presence of TGF-β, IL-21, and IL-23 for the differentiation of Th17 cells. Memory CD4+ T cells were stimulated with IL-1β, IL-6, and IL-23 for the amplification of Th17 cells. IVIG (0.15 mM) was added to the cells 12 h after initiation of cultures. IL-17A cytokine and anti-IL-17 antibodies were measured by ELISA.

Results

IL-23 did not deter the inhibitory effect of IVIG on IL-17 production from the differentiating and expanding Th17 cells. Further, suppression of IL-17 by IVIG did not implicate anti-IL-17 antibodies in the immunoglobulin preparations.

Conclusion

The effect of IVIG on the inhibition of IL-17 production by Th17 cells is a consequence of modulation of Th17 cells and their intracellular signaling pathways and not due to passive neutralization of IL-17 by anti-IL-17 antibodies in the immunoglobulin preparations.

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Acknowledgments

Supported by grants from Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie, Université Paris Descartes and European Community’s Seventh Framework Programme [FP7-2007-2013] under Grant Agreement N° HEALTH-F2-2010-260338-ALLFUN.

Conflict of interest

The research activities on IVIG are partly supported by research grants from Octapharma AG, CSL Behring, Laboratoires Français de Fractionnement et des Biotechnologies, and Talecris Biotherapeutics.

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Authors and Affiliations

  1. Institut National de la Santé et de la Recherche Médicale, Unité 872, 15 rue de l’Ecole de Médicine, Paris, 75006, France

    Mohan S. Maddur, Meenu Sharma, Pushpa Hegde, Sébastien Lacroix-Desmazes, Srini V. Kaveri & Jagadeesh Bayry

  2. Centre de Recherche des Cordeliers, Equipe 16- Immunopathology and therapeutic immunointervention, Université Pierre et Marie Curie – Paris 6, UMR S 872, Paris, 75006, France

    Mohan S. Maddur, Sébastien Lacroix-Desmazes, Srini V. Kaveri & Jagadeesh Bayry

  3. Universite de Technologie de Compiègne, Compiègne, France

    Meenu Sharma & Pushpa Hegde

  4. Université Paris Descartes, UMR S 872, Paris, 75006, France

    Sébastien Lacroix-Desmazes, Srini V. Kaveri & Jagadeesh Bayry

  5. International Associated Laboratory IMPACT (Institut National de la Santé et de la Recherche Médicale, France - Indian Council of Medical Research, India), National Institute of Immunohematology, Mumbai, 400012, India

    Sébastien Lacroix-Desmazes, Srini V. Kaveri & Jagadeesh Bayry

  6. Institut National de la Santé et de la Recherche Médicale, Unité 872, Equipe 16-Centre de Recherche des Cordeliers, 15 rue de l’Ecole de Médicine, Paris, 75006, France

    Srini V. Kaveri & Jagadeesh Bayry

Authors
  1. Mohan S. Maddur
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  2. Meenu Sharma
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  3. Pushpa Hegde
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  4. Sébastien Lacroix-Desmazes
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  5. Srini V. Kaveri
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  6. Jagadeesh Bayry
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Corresponding authors

Correspondence to Srini V. Kaveri or Jagadeesh Bayry.

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Maddur, M.S., Sharma, M., Hegde, P. et al. Inhibitory Effect of IVIG on IL-17 Production by Th17 Cells is Independent of Anti-IL-17 Antibodies in the Immunoglobulin Preparations. J Clin Immunol 33 (Suppl 1), 62–66 (2013). https://doi.org/10.1007/s10875-012-9752-6

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  • DOI: https://doi.org/10.1007/s10875-012-9752-6

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