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

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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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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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    Macroscopic histological sections stained with hematoxylin and eosin (A and C) showing intracerebral 9L tumors in rats treated with either high-dose interleukin-2 (IL-2) (A) or excipient (C). Corresponding images of regional transfer constants are coded to a range of specific values (B and D). The tumor border is outlined by the dotted line in all images. Note the higher transfer constant in the intracerebral tumor of the IL-2-treated animal (A and B); the mean tumor rate constant in this image is 87 mg/gm/min × 10–3. Also note the absence of 14C-AIB activity (that is, blood-brain barrier disruption) in the non-tumor-bearing hemisphere of both animals.

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