Role of interleukin 15 in colitis induced by dextran sulphate sodium in mice.
OBJECTIVE
Interleukin (IL)-15 is a member of the IL-2 family, stimulating dendritic cells, natural killer (NK) cells, NK T cells and memory CD8+ T cells. IL-15 levels were elevated in the intestinal mucosa of inflammatory bowel diseases. Here we investigated the involvement of IL-15 in the pathogenesis of acute and chronic dextran sulphate sodium (DSS) induced colitis.


METHODS
IL-15 knockout (KO) mice and control C57BL/6 mice were used to induce colitis with DSS in their drinking water. Survival rate, clinical activity of diseases, extent of tissue damage, leucocyte population, and cytokine production of lamina propria (LP) cells of the large intestines were assessed.


RESULTS
IL-15 KO mice exhibited resistance to DSS induced acute colitis, as reflected by lower lethality, weight loss, clinical scores, and histological scores compared with those in control mice (p<0.05). The proportions of CD44(high) CD8+ T cells and NK cells in LP cells and levels of interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, and IL-12p40 in culture supernatants of LP cells were reduced in IL-15 KO mice (p<0.05). In vivo depletion of CD8+ T cells and NK cells decreased levels of IFN-gamma, TNF-alpha, and IL-12p40 in culture supernatants of LP cells in C57BL/6 mice (p<0.01). In chronic colitis, weight loss and clinical scores were improved and levels of IFN-gamma, TNF-alpha, and IL-12p40 in culture supernatants of LP cells were also reduced in IL-15 KO mice (p<0.05).


CONCLUSIONS
IL-15 plays an important role in the pathogenesis of both acute and chronic colitis induced by DSS in mice.
Yoshihara
K
K
Division of Host Defence, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Yajima
T
T
Kubo
C
C
Yoshikai
Y
Y
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D003106:Colon / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015996:Survival Rate; D015431:Weight Loss
D016207:Cytokines; D019409:Interleukin-15; D016264:Dextran Sulfate