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.