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

S. Benedetti, B. Pirola, P. L. Poliani, L. Cajola, B. Pollo, R. Bagnati, L. Magrassi, P. Tunici, G. Finocchiaro

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)188-192
Number of pages5
JournalGene Therapy
Volume10
Issue number2
DOIs
Publication statusPublished - Jan 2003

Keywords

  • Dexamethasone
  • Glioma
  • IL-4

ASJC Scopus subject areas

  • Genetics

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