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Interleukin 2 Induced Leukocyte Adhesion to the Normal and Tumor Microvascular Endothelium in Vivo and Its Inhibition by Dextran Sulfate: Implications for Vascular Leak Syndrome¹

Tumor Microcirculation Laboratory, Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213-3890

The maximum dose of interleukin 2 (IL-2) alone or with adoptively transferred lymphocytes is limited by the vascular leak syndrome, resulting from an increase in vascular permeability. Using intravital microscopy to quantify cell interaction in vivo and the Miles assay to assess changes in vascular permeability, we have shown that II-2 increases both leukocyte-endothelial cell adhesion and vascular permeability in the cutaneous tissue of rabbits. Both of these processes can be reversed to a large extent using dextran sulfate (M_r 500,000; 10 mg/kg body weight), a nonspecific blocker of leukocyte-endothelial adhesion. These results suggest that increased leukocyte (probably lymphocyte) adhesion to the postcapillary microvasculature contributes significantly to the IL-2 induced increase in permeability. Therefore, as more specific inhibitors of leukocyte-endothelial adhesion become available, improved strategies could be developed to control or prevent IL-2 toxicity.

¹ Supported by a grant from the American Cancer Society (IM-533) and Alexander von Humboldt Senior Scientist Award (1990-91) to R. K. J. Presented at the 16th European Conference on Microcirculation, Zurich, August 28–31, 1990.

² Present address: The Institute for Public Health, Tokyo 108, Japan. Recipient of a fellowship from the Science and Technology Agency, Japanese government.

³ To whom requests for reprints should be addressed.

Received 11/26/90. Accepted 1/16/91.

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