Interleukin-8 Administration Enhances Venous Thrombosis Resolution in a Rat Model
| Autor: | Manu R. Varma, Thomas W. Wakefield, Minaski Sarkar, Peter K. Henke, Angela E. Hawley, Amy M. Kadell, Marisa J. Linn, Robert M. Strieter, J. Brian Fowlkes |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A medicine.medical_specialty Neutrophils Urology Neovascularization Physiologic Endothelial Growth Factors Inferior vena cava Proinflammatory cytokine Rats Sprague-Dawley Neovascularization Leukocyte Count Fibrosis medicine Animals cardiovascular diseases Thrombus Venous Thrombosis Lymphokines Vascular Endothelial Growth Factors business.industry Interleukin-8 Interleukin medicine.disease Thrombosis Rats Surgery Venous thrombosis medicine.vein Regional Blood Flow Hypertension cardiovascular system Chemokines medicine.symptom business Venous Pressure |
| Zdroj: | Journal of Surgical Research. 99:84-91 |
| ISSN: | 0022-4804 |
| Popis: | Background. Therapy for deep vein thrombosis (DVT) resolution in those patients in whom a complication or contraindication to anticoagulation occurs is limited. As prior work suggests that thrombus maturation involves early influx of neutrophils (PMN) and neovascularization, we hypothesized that administering the proinflammatory/proangiogenic chemokine interleukin (IL)-8 might accelerate thrombus resolution. Materials and methods. An established rodent model of DVT (inferior vena cava [IVC] ligation) was used whereby daily intravenous recombinant human IL-8 (1 μg) or vehicle control was administered, with sacrifice at 4 and 8 days. Prior to sacrifice and at harvest, duplex ultrasound of the DVT and femoral venous pressure measurements were performed. Thrombi were analyzed by immunohistochemical techniques for PMN, monocytes, and neovascularization; for chemokines, by enzyme-linked immunoassay; and fibrosis, by hydroxyproline assay and trichrome staining. Results. IL-8 accelerated thrombus dissolution 4 days after IVC ligation, with 6-fold increased thrombus blood flow by duplex ultrasound and a 23% increased absolute femoral venous pressure compared with controls (both P < 0.05). These findings may be partially explained by the fact that animals receiving IL-8, as compared with controls, had 2.5-fold greater thrombus neovascularization (with a trend continuing to 8 days) and increased PMN at 4 days. Thrombus vascular endothelial growth factor was significantly reduced at 8 days postligation, while monocyte chemotactic protein-1 and macrophage inflammatory protein-1α were not altered by IL-8 administration. At 8 days post-IVC-ligation, fibrosis was 12-fold greater with IL-8 treatment compared with controls. Conclusions. A proinflammatory/proangiogenic thrombus milieu, as conferred by IL-8, enhances thrombus resolution and underscores the important relationship between neovascularity and inflammation. |
| Databáze: | OpenAIRE |
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