Platelet activation and platelet-leukocyte aggregation elicited in experimental colitis are mediated by interleukin-6

• Published in: Inflammatory bowel diseases 2014-02, Vol.20 (2), p.353-362
• Main Authors: Yan, Serena L S, Russell, Janice, Granger, D Neil
• Format: Article
• Language: English
• Subjects: Animals; Cell Adhesion - drug effects; Colitis - drug therapy; Colitis - metabolism; Colitis - pathology; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - metabolism; Inflammatory Bowel Diseases - pathology; Infusions, Intravenous; Interleukin-6 - administration & dosage; Interleukin-6 - pharmacokinetics; Leukocytes; Male; Mice; Mice, Inbred C57BL; Platelet Activation; Recombinant Proteins; Treatment Outcome
• ISSN: 1078-0998; 1536-4844
• DOI: 10.1097/01.MIB.0000440614.83703.84

There is growing evidence for an interdependence of inflammation, coagulation, and thrombosis in acute and chronic inflammatory diseases. Inflammatory bowel diseases (IBD) are associated with a hypercoagulable state and an increased risk of thromboembolism. Although the IBD-associated prothrombogenic state has been linked to the inflammatory response, the mediators that link these 2 conditions remain unclear. Recent evidence suggests that interleukin-6 (IL-6) may be important in this regard. The objective of this study was to more fully define the contribution of IL-6 to the altered platelet function that occurs during experimental colitis. The number of immature and mature platelets, activated platelets, and platelet-leukocyte aggregates were measured in wild-type and IL-6 mice with dextran sodium sulfate (DSS)-induced colonic inflammation. DSS treatment of WT mice was associated with significant increases in the number of both immature and mature platelets, activated platelets, and platelet-leukocyte aggregates. These platelet responses to DSS were not observed in IL-6 mice. Chronic IL-6 infusion (through an Alzet pump) in WT mice reproduced all of the platelet abnormalities observed in DSS-colitic mice. IL-6-infused mice also exhibited an acceleration of thrombus formation in arterioles, similar to DSS. These findings implicate IL-6 in the platelet activation and enhanced platelet-leukocyte aggregate formation associated with experimental colitis, and support a role for this cytokine as a mediator of the enhanced thrombogenesis in IBD.