Association between blood flow and inflammatory state in a T-cell transfer model of inflammatory bowel disease in mice.
BACKGROUND
Adoptive transfer of naive T-lymphocyte subsets into lymphopenic mice initiates chronic gut inflammation that mimics several aspects of inflammatory bowel disease (IBD). Patients with IBD can have profound alterations in intestinal blood flow, but whether the same is true in the T-cell transfer model has yet to be determined.


METHODS
In the current study, chronic intestinal inflammation was induced in recombinase-activating gene-1-deficient (RAG(-/-)) mice by adoptive transfer of CD4(+) T-lymphocytes obtained from interleukin-10 deficient (IL-10(-/-)) mice.


RESULTS
Four weeks later, widespread colonic inflammation was observed in the reconstituted recipients, in contrast to 2 control sets of mice injected with a different subset of lymphocytes or with vehicle alone. We observed that the resulting pathology induced in the reconstituted RAG(-/-) mice was divided distinctly into 2 subsets: 1 with blood flow near normal with very high inflammation scores, and the other with severely attenuated blood flow but with much lower signs of inflammation. Colonic and ileal blood flow rates in the latter subset of CD4(+) mice averaged only approximately 30% compared to the mice with higher inflammation scores. The lower blood flow rates were associated with greatly reduced red blood cell concentrations in the tissue, suggesting a possible loss of vascular density.


CONCLUSIONS
In this model of chronic intestinal inflammation, mild inflammation was associated with significant decreases in blood flow.
Harris
Norman R
NR
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA. nharr6@lsuhsc.edu
Carter
Patsy R
PR
Lee
Seungjun
S
Watts
Megan N
MN
Zhang
Songlin
S
Grisham
Matthew B
MB
D019264:Adoptive Transfer; D000818:Animals; D001783:Blood Flow Velocity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D003106:Colon / Q000098:blood supply*; D004195:Disease Models, Animal; D018398:Homeodomain Proteins / Q000502:physiology; D007082:Ileum / Q000098:blood supply*; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000503:physiopathology*; D016753:Interleukin-10 / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D018398:Homeodomain Proteins; C064658:RAG-1 protein; D016753:Interleukin-10