The effect of interleukin-2 on the blood-brain barrier in the 9L gliosarcoma rat model.
Carbon-14-labeled aminoisobutyric acid was used to determine local blood-to-tissue transfer constants in 22 Fischer rats with intracerebral 9L gliosarcomas that received either high-dose parenteral interleukin-2 (IL-2) or a control injection. In tumor and peritumoral tissue, the transfer constants in the IL-2-treated animals (89.6 +/- 14.6 and 35.8 +/- 6.0, respectively, mean +/- standard error of the mean) were larger (p less than 0.05) than in control animals (61.4 +/- 6.4 and 14.6 +/- 2.2, respectively). In contrast, in normal frontal and occipital tissue contralateral to the tumor-bearing hemisphere, there was no significant difference between the transfer constants in IL-2-treated and control animals. Furthermore, treatment of animals with IL-2 excipient caused no change in permeability as compared to animals treated with Hanks' balanced salt solution. Parenteral injection of IL-2 increases blood-brain barrier disruption in tumor-bearing rat brain but does not increase the vascular permeability of normal brain. Methods to prevent this increased tumor vessel permeability are required before parenteral IL-2 can be used safely for the treatment of primary or metastatic brain tumors.
Alexander
J T
JT
Clinical Neurosurgery Section, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, Maryland.
Saris
S C
SC
Oldfield
E H
EH
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001932:Brain Neoplasms / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism*; D007376:Interleukin-2 / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D007376:Interleukin-2