title: Interleukin-6 mediates the platelet abnormalities and thrombogenesis associated with experimental colitis.
abstract: Clinical studies and animal experimentation have shown that colonic inflammation is associated with an increased number and reactivity of platelets, coagulation abnormalities, and enhanced thrombus formation. The objective of this study was to define the contribution of IL-6 to the thrombocytosis, exaggerated agonist-induced platelet aggregation, and enhanced extra-intestinal thrombosis that occur during experimental colitis. The number of mature and immature platelets, platelet life span, thrombin-induced platelet aggregation response, and light/dye-induced thrombus formation in cremaster muscle arterioles were measured in wild-type (WT) and IL-6-deficient (IL-6(-/-)) mice with dextran sodium sulfate (DSS)-induced colitis. DSS colitis in WT mice was associated with thrombocytosis with an elevated number of both mature and immature platelets and no change in platelet life span. The thrombocytosis response was absent in IL-6(-/-) mice. DSS treatment also enhanced the platelet aggregation response to thrombin and accelerated thrombus development in WT mice, but not in IL-6(-/-) mice. Exogenous IL-6 administered to WT mice elicited a dose-dependent enhancement of thrombus formation. These findings indicate that IL-6 mediates the thrombocytosis, platelet hyperreactivity, and accelerated thrombus development associated with experimental colitis. The IL-6-dependent colitis-induced thrombocytosis appears to result from an enhancement of thrombopoiesis because platelet life span is unchanged.
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-3932, USA.
authors.forename: Elena Y
authors.initials: EY
authors.lastname: Senchenkova
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Komoto
authors.forename: Janice
authors.initials: J
authors.lastname: Russell
authors.forename: Lidiana D
authors.initials: LD
authors.lastname: Almeida-Paula
authors.forename: Li-Sue
authors.initials: LS
authors.lastname: Yan
authors.forename: Songlin
authors.initials: S
authors.lastname: Zhang
authors.forename: D Neil
authors.initials: DN
authors.lastname: Granger
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001791:Blood Platelet Disorders / Q000209:etiology* / Q000378:metabolism; D003092:Colitis / Q000097:blood / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism; D016264:Dextran Sulfate; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010974:Platelet Aggregation; D010976:Platelet Count; D013917:Thrombin / Q000378:metabolism; D013922:Thrombocytosis / Q000209:etiology / Q000378:metabolism; D013927:Thrombosis / Q000209:etiology* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; C577686:interleukin-6, mouse; D016264:Dextran Sulfate; D013917:Thrombin