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The Journal of Immunology, 1998, 161: 1471-1476.
Copyright © 1998 by The American Association of Immunologists

IL-10 Regulates Thrombus-Induced Vein Wall Inflammation and Thrombosis1 ,2

L. Joseph Downing*, Robert M. Strieter{dagger}, Amy M. Kadell*, Carol A. Wilke{dagger}, John C. Austin*, Bradley D. Hare*, Marie D. Burdick{dagger}, Lazar J. Greenfield* and Thomas W. Wakefield3,*

* Section of Vascular Surgery and Jobst Vascular Research Laboratory, Department of Surgery, and {dagger} Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109

Vein wall inflammation associated with venous thrombosis is mediated by an imbalance in proinflammatory as compared with antiinflammatory molecules. We hypothesize that IL-10 is an important antiinflammatory cytokine that influences vein wall inflammation and thrombus propagation during venous thrombosis. To test this hypothesis a model of inferior vena caval thrombosis was used. Studies were performed at sacrifice 2 days after thrombus induction and included leukocyte morphometrics, myeloperoxidase activity, vein wall permeability, thrombus weight, and IL-10 ELISA analysis from the vein wall. IL-10 was elevated in the vein wall during venous thrombosis. Neutralization of IL-10 increased inflammation, while supplementation with rIL-10 demonstrated a dose- and time-dependent decrease in inflammation. Interestingly, a low 2.5-µg rIL-10 dose given at time of initiation of thrombosis most significantly decreased inflammation. Thrombus weight was importantly diminished by reconstitution of IL-10. These studies support an important role for IL-10 in the regulation of thrombus-associated inflammation and thrombosis and suggest that IL-10 could be used as a therapeutic agent in the treatment of venous thrombosis.




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