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Interleukin 2 Acutely Induces Platelet and Neutrophil-Endothelial Adherence and Macromolecular Leakage¹

Division of Surgical Oncology, Departments of Surgery [M. J. E., D. L. A.], Physiology [F. N. M., D. A. S.], and Pathology [T. S. C.], University of Louisville School of Medicine, Louisville, Kentucky 40292, and the Department of Anatomy and Physiology [D. E. S.], Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Prince Edward Island, Canada, C1A 4P3

The acute effects of interleukin 2 (IL-2) were determined in the rat cremaster microcirculation model by intravital, light, and electron microscopy to better understand the pathophysiology of the IL-2-induced vascular leak syndrome. Four groups of rats were studied over a 2-h monitoring period. One group received 1 x 10⁴ units of IL-2/kg i.v. (n = 10), while the remaining groups received IL-2 topically applied to the cremaster muscle in dosages of either 1 x 10⁵ (n = 9), 1 x 10⁶ (n = 5), or 3 x 10⁶ (n = 5) units. Each group was compared with controls (n = 9). IL-2 administered i.v. acutely induced platelet and polymorphonuclear leukocyte-endothelial adherence and microvascular macromolecular leakage that occurred synchronous with the development of tachycardia, hypotension, tachypnea, and hypoxemia. Topically applied IL-2 induced similar microvascular alterations but without changes in hemodynamic and respiratory parameters, which suggests that microvascular alterations were not caused by IL-2-induced changes in hemodynamic parameters. Electron microscopy of cremaster muscle sections demonstrated platelet and neutrophil adherence to the endothelium and endothelial injury. We conclude that IL-2 (or a locally generated mediator) acutely induces platelet and neutrophil-endothelial adherence in the rat skeletal muscle microcirculation that is associated with the development of macromolecular leakage from the microcirculation.

¹ Supported by American Cancer Society Clinical Oncology Career Development Award (CDA-90-178) (M. J. E.). Ultrastructural portions of this study were supported by a grant from the Heart and Stroke Foundation of Canada (D. E. S.).

² To whom requests for reprints should be addressed, at the Department of Surgery, University of Louisville, Louisville, KY 40292.

Received 6/26/91. Accepted 4/ 3/92.

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