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Subcutaneous injection of interleukin 12 induces systemic inflammatory responses in humans: implications for the use of IL-12 as vaccine adjuvant

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Abstract

Interleukin 12 (IL-12) is a cytokine with important regulatory functions bridging innate and adaptive immunity. It has been proposed as an immune adjuvant for vaccination therapy of infectious diseases and malignancies. The inflammatory properties of IL-12 play an important role in the adjuvant effect. We studied the effect of s.c. injections of recombinant human IL-12 (rHuIL-12) in 26 patients with renal cell cancer and demonstrated dose-dependent systemic activation of multiple inflammatory mediator systems in humans. rHuIL-12 at a dose of 0.5 μg/kg induced degranulation of neutrophils with a significant increase in the plasma levels of elastase (p<0.05) and lactoferrin (p=0.01) at 24 h. Additionally, rHuIL-12 injection mediated the release of lipid mediators, as demonstrated by a sharp increase in the plasma secretory phospholipase A2 (sPLA2) level (p=0.003). rHuIL-12, when administered at a dose of 0.1 μg/kg, showed minimal systemic effects. In conclusion, when IL-12 is used as an adjuvant, doses should not exceed 0.1 μg/kg, in order to avoid severe systemic inflammatory responses.

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Authors and Affiliations

  1. Department of Medical Oncology, Erasmus Medical Center, Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands

    Johanna E. A. Portielje, Wim H. J. Kruit, Alex Sparreboom & Gerrit Stoter

  2. Department of Immunopathology, CLB Sanquin Foundation, Amsterdam, The Netherlands

    Anke J. M. Eerenberg & C. Erik Hack

  3. Department of Medicine III, Johannes Gutenberg University, Mainz, Germany

    Martin Schuler & Christoph Huber

  4. Department of Medical and Tumor Immunology, Erasmus Medical Center, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands

    Cor H. J. Lamers & Jan-Willem Gratama

  5. VU Medical Center, Amsterdam, The Netherlands

    C. Erik Hack

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  1. Johanna E. A. Portielje
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  2. Wim H. J. Kruit
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  3. Anke J. M. Eerenberg
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Correspondence to Wim H. J. Kruit.

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Portielje, J.E.A., Kruit, W.H.J., Eerenberg, A.J.M. et al. Subcutaneous injection of interleukin 12 induces systemic inflammatory responses in humans: implications for the use of IL-12 as vaccine adjuvant. Cancer Immunol Immunother 54, 37–43 (2005). https://doi.org/10.1007/s00262-004-0574-0

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