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Dexamethasone inhibits the anti-tumor effect of interleukin 4 on rat experimental gliomas

Gene Therapy volume 10, pages 188–192 (2003)Cite this article

Abstract

Retroviral-mediated gene transfer of the IL-4 gene into experimental gliomas can cause tumor rejection, supporting the clinical use of this form of gene therapy for glioblastomas (GBM). In a clinical setting, the administration of dexamethasone (dex) is a standard procedure for GBM patients. This led us to examine the effects of dex on IL-4 gene therapy. We injected intracranially Fischer 344 rats with phosphate-buffered saline, 9L gliosarcoma cells mixed with E86.L4SN200 cells (retroviral producer cells, RPC, transducing IL-4 cDNA) and 9L cells mixed with PA317.STK.SBA cells (control RPC expressing the HSV-tk gene). The rats from each group were treated with 0, 50, 100 or 250 μg dex/kg/day released by osmotic pumps implanted subcutaneously. While 80–100% of rats receiving 9L cells mixed with IL-4 RPC and not treated by dex survived for at least 2 months following tumor injection, only 50% and 17% of rats receiving 50 or 100 μg/kg/day of dex, respectively, reached this time point. These results indicate that dex significantly diminished the anti-tumor effect of IL-4. Thus, in a clinical setting, IL-4 gene transfer should be performed when low levels of dex are administered or in the absence of dex.

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Acknowledgements

This study was supported by research grants from the Italian Minister of Health (‘Ricerca Finalizzata’) and from the Associazione Italiana per la Ricerca sul Cancro (AIRC) to GF.

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Authors and Affiliations

  1. Istituto Neurologico Besta, Milan, 20133, Italy

    S Benedetti, B Pirola, P L Poliani, L Cajola, B Pollo, P Tunici & G Finocchiaro

  2. Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy

    R Bagnati

  3. Department of Surgery, Policlinico S. Matteo, University of Pavia, Italy

    L Magrassi

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  1. S Benedetti
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Benedetti, S., Pirola, B., Poliani, P. et al. Dexamethasone inhibits the anti-tumor effect of interleukin 4 on rat experimental gliomas. Gene Ther 10, 188–192 (2003). https://doi.org/10.1038/sj.gt.3301863

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