Supported by the “Fondazione Umberto di Mario,” Rome, the Broad Medical Research Program Foundation (No. IBD-0242), and Giuliani SpA, Milan, Italy.
Version of Record online: 17 JUN 2011
Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 18, Issue 3, pages 449–459, March 2012
How to Cite
Rizzo, A., Monteleone, I., Fina, D., Stolfi, C., Caruso, R., Fantini, M. C., Franzè, E., Schwendener, R., Pallone, F. and Monteleone, G. (2012), Inhibition of colitis by IL-25 associates with induction of alternatively activated macrophages. Inflamm Bowel Dis, 18: 449–459. doi: 10.1002/ibd.21799
Declaration: G.M. has filed a patent entitled “A treatment for inflammatory diseases”“ (patent No. 08154101.3), while the remaining authors have no conflicts of interest to disclose.
- Issue online: 13 FEB 2012
- Version of Record online: 17 JUN 2011
- Manuscript Accepted: 19 MAY 2011
- Manuscript Received: 28 APR 2011
- Crohn's disease;
Interleukin (IL)-25, a Th2-related factor, inhibits the synthesis of inflammatory cytokines by macrophages and attenuates experimental colitis in mice. The mechanism underlying the counterregulatory effect of IL-25, however, remains unknown. Since Th2-cytokines can abrogate inflammatory pathways by inducing alternatively activated macrophages (AAMs), we evaluated whether AAMs are involved in the IL-25-mediated anticolitic effect.
AAM-related markers were evaluated in peritoneal and lamina propria mononuclear cells of mice with or without 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced colitis treated with IL-25 and/or neutralizing IL-4, IL-13, and transforming growth factor beta 1 (TGF-β1) antibodies. Peritoneal AAMs induced in vivo by injecting mice with IL-25 were transferred to mice with TNBS colitis. Finally, we assessed the in vitro effect of IL-25 on the alternative activation of peritoneal F4/80+ cells.
IL-25 enhanced the expression of AAM-related markers in F4/80+ cells infiltrating the peritoneum and colon of naïve and colitic mice. Peritoneal F4/80+ cells isolated from IL-25-treated mice reduced the severity of TNBS colitis when injected intraperitoneally to recipient mice. Since IL-25 did not directly induce AAM in vitro and in vivo in mice, IL-25 administration enhanced the expression of IL-4, IL-13, and TGF-β1, which are known to promote AAM differentiation, we finally assessed whether such cytokines were involved in the IL-25-driven AAM induction. Blockade of IL-4, IL-13, and TGF-β1 with neutralizing antibodies in mice did not inhibit the stimulatory effect of IL-25 on AAM gene expression.
The IL-25-mediated anticolitic effect is associated with induction of AAMs, a subset of macrophages with antiinflammatory properties. (Inflamm Bowel Dis 2012;)