title: Platelet activation and platelet-leukocyte aggregation elicited in experimental colitis are mediated by interleukin-6.
abstract: 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.
authors.affiliation: Department of Molecular and Cellular Physiology, LSU Health Sciences Center, Shreveport, Louisiana.
authors.forename: Serena L S
authors.initials: SL
authors.lastname: Yan
authors.forename: Janice
authors.initials: J
authors.lastname: Russell
authors.forename: D Neil
authors.initials: DN
authors.lastname: Granger
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D003092:Colitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007962:Leukocytes; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015539:Platelet Activation; D011994:Recombinant Proteins; D016896:Treatment Outcome
chemical_list: D015850:Interleukin-6; D011994:Recombinant Proteins; C577686:interleukin-6, mouse