Role of tumor necrosis factor-α in the extraintestinal thrombosis associated with colonic inflammation
Open Access
- 1 November 2011
- journal article
- research article
- Published by Oxford University Press (OUP) in Inflammatory Bowel Diseases
- Vol. 17 (11), 2217-2223
- https://doi.org/10.1002/ibd.21593
Abstract
Inflammatory bowel diseases (IBDs) are associated with a hypercoagulable state and an increased risk of thromboembolism, with accelerated thrombus formation occurring both within the inflamed bowel and in distant tissues. While the IBD-associated prothrombogenic state has been linked to the inflammatory response, the mediators that link inflammation and thrombosis remain poorly defined. The objective of this study was to assess the role of tumor necrosis factor alpha (TNF-α) in the enhanced extraintestinal microvascular thrombosis that accompanies colonic inflammation. TNF-α concentration was measured in plasma, colon, and skeletal muscle of control mice and in mice with dextran sodium sulfate (DSS)-induced colitis. A light/dye injury method was used to induce microvascular thrombosis in cremaster microvessels. The effects of exogenous TNF-α on thrombus formation were determined in control mice. DSS-enhanced thrombus formation was evaluated in wildtype (WT) mice treated with an anti-TNF-α antibody (±an anti-IL-1β antibody) and in TNF-α receptor-deficient (TNFr−/−) mice. DSS colitis enhanced thrombus formation in cremaster arterioles. A similar response was produced by TNF-α administration in control mice. TNF-α concentration was elevated in plasma, colon, and skeletal muscle. Immunoblockade of TNF-α or genetic deficiency of the TNF-α receptor blunted the thrombotic response of arterioles to DSS colitis. Additional protection was noted in mice receiving antibodies to both TNF-α and IL-1β. Our findings implicate TNF-α in the enhanced microvascular thrombosis that occurs in extraintestinal tissue during colonic inflammation, and suggests that the combined actions of TNF-α and IL-1β accounts for most of the colitis-enhanced thrombotic response. (Inflamm Bowel Dis 2010;)Keywords
This publication has 28 references indexed in Scilit:
- Interleukin-1β Mediates the Extra-Intestinal Thrombosis Associated with Experimental ColitisThe American Journal of Pathology, 2010
- Inflammatory bowel diseaseInflammatory Bowel Diseases, 2009
- The effect of proteasome inhibitor MG132 on experimental inflammatory bowel diseaseClinical and Experimental Immunology, 2009
- Thrombin mediates the extraintestinal thrombosis associated with experimental colitisAmerican Journal of Physiology-Gastrointestinal and Liver Physiology, 2008
- Role of the Protein C Pathway in the Extraintestinal Thrombosis Associated With Murine ColitisGastroenterology, 2008
- Crucial role of the protein C pathway in governing microvascular inflammation in inflammatory bowel diseaseJCI Insight, 2007
- Tissue factor: a mediator of inflammatory cell recruitment, tissue injury, and thrombus formation in experimental colitisThe Journal of Experimental Medicine, 2007
- Systemic Thromboembolism in Inflammatory Bowel Disease: Mechanisms and Clinical ApplicationsAnnals of the New York Academy of Sciences, 2005
- In Vitro Role of IL-1 in Heightened IgG, Anti-DNA, and Nephritogenic Idiotype Production by B Cells Derived from the Murine MRL/lpr Lupus ModelClinical Immunology and Immunopathology, 1994
- Modulation of endothelial cell hemostatic properties by tumor necrosis factor.The Journal of Experimental Medicine, 1986