Interleukin-8 administration enhances venous thrombosis resolution in a rat model?

Background Therapy far deep vein thrombosis (DVT) resolution in those patie nts in whom a complication or contraindication, to anticoagulation occurs i s Limited. As prior work suggests that thrombus maturation involves early i nflux of neutrophils (PMN) and neovascularization, we hypothesized that adm inistering the proinflammatory/proangiolenic chemokine interleukin (IL)-8 m ight accelerate thrombus resolution. Materials and methods. An established rodent model of DVT (inferior vena ca va [IVC] ligation) was used whereby daily intravenous recombinant human IL- 8 (1 mug) or vehicle control was administered, with sacrifice at 4 and 8 da ys. Prior to sacrifice and at harvest, duplex ultrasound of the DVT and fem oral venous pressure measurements mere performed. Thrombi were analyzed by immunohistochemical techniques for PMN, monocytes, and neovascularization; for chemokines, by enzyme-linked immunoassay; and fibrosis, by hydroxyproli ne assay and trichrome staining. Results. IL-8 accelerated thrombus dissolution 4 days after IVC ligation, w ith 6-fold increased thrombus blood flow by duplex ultrasound and a 23% inc reased absolute femoral venous pressure compared with controls (both P < 0. 05). These findings may be partially explained by the fact that animals rec eiving IL-8, as compared with controls, had 2.5-fold greater thrombus neova scularization (with a trend continuing to 8 days) and increased PMN at 4 da ys. Thrombus vascular endothelial growth factor was significantly reduced a t 8 days postligation, while monocyte chemotactic protein-1 and macrophage inflammatory protein-1<alpha> were not altered by IL-8 administration. At 8 days post-TVC-ligation, firosis was 12-fold greater with IL-8 treatment co mpared with controls. Conclusions. A proinflammatory/proangiogenic thrombus milieu, as conferred by IL-8, enhances thrombus resolution and underscores the important relatio nship between neovascularity and inflammation. (C) 2001 Academic Press.