Interleukin 10-deficient colitis: new similarities to human inflammatory bowel disease.
BACKGROUND
Interleukin (IL) 10 is a potent anti-inflammatory cytokine. Disruption of the IL-10 gene in C57/Black6 mice results in enterocolitis in the presence of intestinal bacteria. This study investigated gut mucosal barrier function sequentially during the development of colitis in this model.


METHODS
Animals were bred in specific pathogen-free conditions and transferred to conventional housing at 4 weeks. Mice were evaluated at 6, 8, 10, 12, 14 and 15 weeks of age. Barrier function was assessed by measuring intestinal permeability and antibody response to systemic endotoxaemia (antibody to the core glycolipid region of lipopolysaccharide; EndoCAb). Colons were harvested and a histological injury score (HIS) was calculated.


RESULTS
The HIS increased progressively until 12 weeks, with an associated increase in intestinal permeability, and immunoglobulin (Ig) M and IgG EndoCAb. The HIS correlated positively with both intestinal permeability and IgM and IgG EndoCAb. Intestinal permeability showed a positive correlation with EndoCAb.


CONCLUSIONS
IL-10 knockout mice develop colitis with an associated disturbance in gut mucosal barrier function, as measured by increased permeability and endotoxaemia. The colitis found in the IL-10 knockout mouse shares these histological, physiological and biochemical features with human inflammatory bowel disease and is therefore suitable for therapeutic trials. A measure of endotoxaemia correlated directly with intestinal permeability in this model.
Kennedy
R J
RJ
Departments of Surgery and Pathology, Institute of Clinical Science, Queen's University of Belfast, Grosvenor Road, Belfast BT12 6BJ, UK.
Hoper
M
M
Deodhar
K
K
Erwin
P J
PJ
Kirk
S J
SJ
Gardiner
K R
KR
D000818:Animals; D003092:Colitis / Q000209:etiology* / Q000473:pathology; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016753:Interleukin-10