IL-10 REGULATES THROMBUS-INDUCED VEIN WALL INFLAMMATION AND THROMBOSIS

Vein wall inflammation associated with venous thrombosis is mediated b y an imbalance in proinflammatory as compared with antiinflammatory mo lecules. We hypothesize that IL-10 is an important antiinflammatory cy tokine 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, m yeloperoxidase activity, vein wall permeability, thrombus weight, and IL-10 ELISA analysis from the vein wall. IL-10 was elevated in the vei n wall during venous thrombosis. Neutralization of IL-10 increased inf lammation, while supplementation with rIL-10 demonstrated a dose- and time-dependent decrease in inflammation. Interestingly, a low 2.5-mu g rIL-10 dose given at time of initiation of thrombosis most significan tly decreased inflammation. Thrombus weight was importantly diminished by reconstitution of IL-10. These studies support an important role f or IL-10 in the regulation of thrombus-associated inflammation and thr ombosis and suggest that IL-10 could be used as a therapeutic agent in the treatment of venous thrombosis.