Dexamethasone inhibits the anti-tumor effect of interleukin 4 on rat experimental gliomas.
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.L4SN(200) 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 microg 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 microg/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.
Benedetti
S
S
Laboratory of Neuro-Oncology and Gene Therapy, Istituto Nazionale Neurologico Besta, Via Celoria 11, 20133 Milan, Italy.
Pirola
B
B
Poliani
P L
PL
Cajola
L
L
Pollo
B
B
Bagnati
R
R
Magrassi
L
L
Tunici
P
P
Finocchiaro
G
G
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D000075202:Contraindications; D003907:Dexamethasone / Q000494:pharmacology; D004343:Drug Implants; D005822:Genetic Vectors / Q000008:administration & dosage; D018316:Gliosarcoma / Q000276:immunology / Q000628:therapy*; D015847:Interleukin-4 / Q000235:genetics* / Q000276:immunology; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D051381:Rats; D011916:Rats, Inbred F344; D012190:Retroviridae / Q000235:genetics
D018931:Antineoplastic Agents, Hormonal; D004343:Drug Implants; D015847:Interleukin-4; D003907:Dexamethasone