title: IL-6 Mediates the Intestinal Microvascular Thrombosis Associated with Experimental Colitis.
abstract: Inflammatory bowel diseases are associated with increased risk for thrombus formation both within the inflamed bowel and at distant sites. Although the increased propensity for distant organ thrombus development has been recapitulated in animal models of colitis and linked to interleukin-6 (IL-6), it remains unclear whether experimental colitis results in accelerated thrombus development within the inflamed bowel and whether IL-6 contributes to a local thrombogenic response. These issues related to thrombus formation within the inflamed bowel were addressed in mice with dextran sodium sulfate-induced colitis. Wild-type (WT) mice, IL-6 deficient (IL-6(-/-)) mice, and bone marrow chimeras (WT→WT and IL-6(-/-)→WT) were used. The effects of treatment with either an IL-6-blocking, IL-6Rα-blocking or gp130-blocking antibody were also evaluated. Disease activity index and colonic weight-to-length ratio (W/L) were used to monitor the development of colitis. Intravital videomicroscopy was used to study thrombus development (induced with the light/dye method) in mucosal vessels of the ascending colon. Thrombus development was significantly enhanced in WT colitic mice. Neither genetic deficiency nor immunoblockade of IL-6 significantly altered the disease activity index and W/L responses to dextran sodium sulfate treatment. However, colitis-induced thrombogenesis was attenuated in IL-6(-/-) mice and in WT mice treated with either the IL-6-blocking, IL-6Rα-blocking or gp130-blocking antibody. IL-6(-/-)→WT, but not WT→WT chimeras, exhibited a blunted thrombosis response to dextran sodium sulfate. These results indicate that experimental colitis is associated with accelerated thrombus development within the inflamed colon and that IL-6, derived from bone marrow-derived blood cells, is largely responsible for this response.
authors.affiliation: *Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana; and †Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hozumi
authors.forename: Janice
authors.initials: J
authors.lastname: Russell
authors.forename: Shantel
authors.initials: S
authors.lastname: Vital
authors.forename: D Neil
authors.initials: DN
authors.lastname: Granger
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity*; D005260:Female; D015850:Interleukin-6 / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply / Q000473:pathology*; D000069416:Intravital Microscopy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013927:Thrombosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology
chemical_list: D015850:Interleukin-6; D016264:Dextran Sulfate