Mice deficient in Th1- and Th2-type cytokines develop distinct forms of hapten-induced colitis.
OBJECTIVE
Most experimental models for inflammatory bowel disease in mice are associated with production of interferon (IFN)-gamma and other proinflammatory cytokines. We hypothesized that T-helper 2 (Th2)-type cells could also contribute to the colitis and cause inflammation different than that mediated by Th1-type cells.


METHODS
Trinitrobenzene sulfonic acid (TNBS)-induced colitis in C57BL/6 background mice genetically deficient in interleukin (IL)-12 p40 (IL-12(-/-)), IFN-gamma (IFN-gamma(-/-)), or IL-4 (IL-4(-/-)) was examined in comparison with control mice (C57BL/6(+/+)).


RESULTS
C57BL/6(+/+), IFN-gamma(-/-), and IL-12(-/-) mice developed patterns of colitis characterized by distortion of crypts, loss of goblet cells, and mononuclear cell infiltration with fibrosis of the mucosal layer. IL-4(-/-) mice had greater mortality than other groups because of penetrating ulcers; however, survivors developed milder lesions that were limited to focal acute ulceration. Colonic CD4(+) T cells from normal, IFN-gamma(-/-), or IL-12(-/- )mice produced both IL-4 and IL-5.


CONCLUSIONS
In TNBS colitis, Th1-like cytokine responses induce fatal, acute, transmural, and focal types of lesions, whereas Th2-like cytokine responses play a significant role in the diffuse atrophic changes in crypts and the mucosal layer that occur in the late stages of this disease.
Dohi
T
T
Immunobiology Vaccine Center, University of Alabama at Birmingham, Birmingham, Alabama, USA. dohi@ri.imcj.go.jp
Fujihashi
K
K
Kiyono
H
H
Elson
C O
CO
McGhee
J R
JR
D000818:Animals; D000906:Antibodies / Q000032:analysis; D000918:Antibody Specificity; D001284:Atrophy; D003092:Colitis / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D003106:Colon / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000172:deficiency*; D004198:Disease Susceptibility; D004733:Enema; D007371:Interferon-gamma / Q000097:blood; D007413:Intestinal Mucosa / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*; D014302:Trinitrobenzenesulfonic Acid / Q000008:administration & dosage / Q000276:immunology
D000906:Antibodies; D016207:Cytokines; D007371:Interferon-gamma; D014302:Trinitrobenzenesulfonic Acid