The effect of interleukin-2 on the blood-brain barrier in the 9L gliosarcoma rat model

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  • 1 Clinical Neurosurgery Section, Surgical Neurology Branch, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, Maryland
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✓ 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 < 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.

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Contributor Notes

Address reprint requests to: Stephen C. Saris, M.D., 9000 Rockville Pike, National Institutes of Health, Building 10, Room 5D-37, Bethesda, Maryland 20892.
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