Low Molecular Weight Heparin Suppresses Tumor Necrosis Factor Expression from Deep Vein Thrombosis

Abstract

Prior investigations have shown that low molecular weight heparin (LMWH) possesses anti-inflammatory properties in addition to its anticoagulant effects. The physiology of this anti-inflammatory mechanism is poorly understood. Experiments were performed to assess the in vivo anti-inflammatory effects of LMWH in a rat model of deep vein thrombosis (DVT). Sprague-Dawley rats were divided into three groups and underwent laparotomy and inferior vena cava (IVC) ligation directly below the renal veins to induce thrombosis. Twenty-four hours later, intraluminal clot was confirmed at repeat laparotomy using an electromagnetic flowmeter and visual inspection. An intravenous infusion of LMWH or urokinase or no infusion (control) was then performed. Subcutaneous LMWH was given postoperatively to the heparin group. Twenty-four hours after the second operation, the animals were killed, the IVC harvested, the cells from the IVC purified, and cytokine measurements done. The LMWH group showed an overall statistically significant decrease in tumor necrosis factor-alpha (TNF-alpha) levels compared to both the control and urokinase groups by analysis of variance (918 pg/mL vs. 1,345 and 1,623, respectively; P = 0.001). To ensure accuracy, individual pairwise comparisons were performed, which also showed statistically significant TNF-alpha suppression by LMWH compared to control (P = 0.015) and urokinase (P = 0.0009). Treatment of DVT with LMWH causes suppression of TNF-alpha expression. This may, in part, explain its anti-inflammatory effects.