The role of interleukin-15 in colitis induced by dextran sulphate sodium in mice

Kazufumi Yoshihara ¹, Toshiki Yajima ^1*, Chiharu Kubo ² and Yasunobu Yoshikai ¹

¹ Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Japan
² Department of Psychosomatic Medicine, Medical Institute of Bioregulation, Kyushu University, Japan

^* To whom correspondence should be addressed. E-mail: yajimato{at}bioreg.kyushu-u.ac.jp.

Accepted 31 August 2005

Abstract

Background and aims: Interleukin (IL)-15 is a member of the IL-2 receptor family, stimulating dendritic cells, natural killer (NK) cells, NKT cells and memory CD8⁺ T cells. IL-15 level was 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, leukocyte 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 the levels of interferon (IFN)-, tumor 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 the levels of IFN-, TNF-, 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 the levels of IFN-, TNF-, and IL-12p40 in culture supernatants of LP cells were also reduced in IL-15 KO mice (p<0.05).

Conclusions: IL-15 plays important roles in the pathogenesis of both acute and chronic colitis induced by DSS in mice.

Keywords: colitis, dextran sulphate, interleukin-15, mice

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