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Interleukin-6 protects against paclitaxel, cisplatin and vincristine-induced neuropathies without impairing chemotherapeutic activity

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Abstract

Purpose

This study was conducted to investigate the potential neuroprotective effect of IL-6 on chemotherapy induced neuropathy (CIN). IL-6 was compared to four-methylcatechol (4-MC)-a known inducer of NGF secretion previously shown to exhibit neuroprotective effects in CIN models.

Methods

Three CIN models were used; two in rats (cisplatin and vincristine) and one in mice (paclitaxel). IL-6 was delivered in four different doses in rats (0.3, 1, 3, 10 μg/kg, sc) every day from the first day of chemotherapeutic agent intoxication until the end of the study (day 37 for cisplatin protocol and day 30 for vincristine procedure). In mice, IL-6 was delivered at 10 μg/kg, sc either daily or three times a week from the first day of intoxication until the end of the study (day 19). Behavioral testings (hot plate and rotarod), nerve conduction studies (CMAP, SNCV, H-wave) and histo-morphometric analysis were done for all models. In addition, we tested whether IL-6 interfered with the tumor-reducing effects of the chemotherapeutic agents.

Results

IL-6 treatment prevented the behavioral and electrophysiological abnormalities produced by vincristine, cisplatin and Taxol intoxication, and similarly prevented the pathological changes in peripheral nerves. The neuroprotective action of chronic IL-6 treatment was at least equal to that of 4-MC. In addition, IL-6 neither inhibited the antitumour activity of cisplatin, nor stimulated tumour growth.

Conclusion

IL-6 at low doses (10 μg/kg) provided protection against the development of CIN without demonstrating interference with the anti tumoural activity of these anti-mitotic drugs.

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Acknowledgments

This study is supported in part by research funding from Merck Serono International to NC. We would like to thank Hagit Krug and Judith Chebath for scientific input during this collaboration as well as Judith Abdalla and Debbie Saunders for their sustained support of the project.

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Authors and Affiliations

  1. Neurofit, rue Jean Sapidus, Parc d’Innovation, 67400, Illkirch, France

    Noelle Callizot & Emile Andriambeloson

  2. Emory Center for Neurodegenerative Diseases, Atlanta, GA, 30322, USA

    Jonathan Glass

  3. Weizmann Institute, Rehovot, Israel

    Michel Revel

  4. Instituto di Ricerche Biomediche ‘‘Antoine Marxer’’ RBM S.p.a, 10010, Colleretto Giacosa (Torino), Italy

    Pamela Ferro & Rocco Cirillo

  5. Merck Serono Research Institute, Chemin des Mines 9, 1202, Geneva, Swizterland

    Pierre-Alain Vitte

  6. Merck Serono International SA, Chemin des Mines 9, 1202, Geneva, Swizterland

    Michel Dreano

  7. Royal Arsenal, Building49-Flat15, Argyll road, London, SE186XB, UK

    Noelle Callizot

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  1. Noelle Callizot
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  2. Emile Andriambeloson
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  3. Jonathan Glass
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  4. Michel Revel
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  7. Pierre-Alain Vitte
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Correspondence to Noelle Callizot.

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Callizot, N., Andriambeloson, E., Glass, J. et al. Interleukin-6 protects against paclitaxel, cisplatin and vincristine-induced neuropathies without impairing chemotherapeutic activity. Cancer Chemother Pharmacol 62, 995–1007 (2008). https://doi.org/10.1007/s00280-008-0689-7

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  • DOI: https://doi.org/10.1007/s00280-008-0689-7

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