Role of interleukin 15 in colitis induced by dextran sulphate sodium in mice
- 1Division of Host Defence, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
- 2Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
- Correspondence to:
Dr Toshiki Yajima
Division of Host Defence, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan;
- Accepted 31 August 2005
- Revised 11 August 2005
- Published Online First 14 September 2005
Background and aims: 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 CD44high CD8+ T cells and NK cells in LP cells and levels of interferon (IFN)-γ, tumour necrosis factor (TNF)-α, 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-γ, TNF-α, 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-γ, TNF-α, 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.
- IL, interleukin
- NK, natural killer
- DSS, dextran sulphate sodium
- KO, knockout
- LP, lamina propria
- IFN, interferon
- TNF, tumour necrosis factor, IBD, inflammatory bowel disease
- CD, Crohn’s disease
- UC, ulcerative colitis
- Th1, T helper type 1
- DC, dendritic cell
- FCM, flow cytometry
- FITC, fluorescein isothiocyanate
- mAb, monoclonal antibody
- PE, phycoerythrin
- APC, allophycocyanin
- ELISA, enzyme linked immunosorbent assay
- TCR, T cell receptor
- WT, wild-type
- FBS, fetal bovine serum
Published online first 14 September 2005
Conflict of interest: None declared.