Interleukin 2 induced leukocyte adhesion to the normal and tumor microvascular endothelium in vivo and its inhibition by dextran sulfate: implications for vascular leak syndrome
Ohkubo, C.; Bigos, D.; Jain, R.K.
Cancer Research 51(5): 1561-1563
1991
ISSN/ISBN: 0008-5472 PMID: 1997196 Document Number: 381154
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 IL-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 (Mr approximately 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.