Serum biomarkers in a mouse model of bacterial-induced inflammatory bowel disease.
BACKGROUND
The diagnosis and classification of inflammatory bowel disease (IBD) require both clinical and histopathologic data. Serum biomarkers would be of considerable benefit to noninvasively monitor the progression of disease, assess effectiveness of therapies, and assist in understanding disease pathogenesis. Currently, there are limited noninvasive biomarkers for monitoring disease progression in animal IBD models, which are used extensively to develop new therapies and to understand IBD pathogenesis.


METHODS
Serum biomarkers of early and late IBD were identified using multianalyte profiling in mdr1a(-/-) mice with IBD triggered by infection with Helicobacter bilis. The correlation of changes in these biomarkers with histopathology scores and clinical signs in the presence and in the absence of antibiotic treatment was determined.


RESULTS
Serum levels of interleukin (IL)-11, IL-17, 10-kDa interferon-gamma-inducible protein (IP-10), lymphotactin, monocyte chemoattractant protein (MCP)-1, and vascular cell adhesion molecule (VCAM)-1 were elevated early in IBD. In late, more severe IBD, serum levels of IL-11, IP-10, haptoglobin, matrix metalloproteinase-9, macrophage inflammatory protein (MIP)-1gamma, fibrinogen, immunoglobulin A, MIP-3 beta (beta), VCAM-1, apolipoprotein (Apo) A1, and IL-18 were elevated. All late serum biomarkers except Apo A1 correlated with histopathology scores. Antibiotic treatment improved clinical signs of IBD and decreased mean serum values of many of the biomarkers. For all biomarkers, the individual pathology scores correlated significantly with individual serum analyte levels after treatment.


CONCLUSIONS
Serum analyte measurement is a useful, noninvasive method for monitoring disease in a mouse model of bacterial-induced IBD.
Torrence
Anne E
AE
Washington National Primate Research Center, University of Washington, Seattle, Washington 98195, USA. aminard@u.washington.edu
Brabb
Thea
T
Viney
Joanne L
JL
Bielefeldt-Ohmann
Helle
H
Treuting
Piper
P
Seamons
Audrey
A
Drivdahl
Rolf
R
Zeng
Weiping
W
Maggio-Price
Lillian
L
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D016481:Helicobacter Infections / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis* / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains
D000900:Anti-Bacterial Agents; D015415:Biomarkers