TY - JOUR T1 - Non-redundant properties of IL-1α and IL-1β during acute colon inflammation in mice JF - Gut JO - Gut SP - 598 LP - 609 DO - 10.1136/gutjnl-2012-303329 VL - 63 IS - 4 AU - Marina Bersudsky AU - Lotem Luski AU - Daniel Fishman AU - Rosalyn M White AU - Nadya Ziv-Sokolovskaya AU - Shahar Dotan AU - Peleg Rider AU - Irena Kaplanov AU - Tegest Aychek AU - Charles A Dinarello AU - Ron N Apte AU - Elena Voronov Y1 - 2014/04/01 UR - http://gut.bmj.com/content/63/4/598.abstract N2 - Objective The differential role of the IL-1 agonists, IL-1α, which is mainly cell-associated versus IL-1β, which is mostly secreted, was studied in colon inflammation. Design Dextran sodium sulfate (DSS) colitis was induced in mice globally deficient in either IL-1α or IL-1β, and in wild-type mice, or in mice with conditional deletion of IL-1α in intestinal epithelial cells (IECs). Bone marrow transplantation experiments were performed to assess the role of IL-1α or IL-1β of myeloid versus colon non-hematopoietic cells in inflammation and repair in acute colitis. Results IL-1α released from damaged IECs acts as an alarmin by initiating and propagating colon inflammation, as IL-1α deficient mice exhibited mild disease symptoms with improved recovery. IL-1β is involved in repair of IECs and reconstitution of the epithelial barrier during the resolution of colitis; its deficiency correlates with disease exacerbation. Neutralisation of IL-1α in control mice during acute colitis led to alleviation of clinical and histological manifestations, whereas treatment with rIL-1Ra or anti-IL-1β antibodies was not effective. Repair after colitis correlated with accumulation of CD8 and regulatory T cells in damaged crypts. Conclusions The role of IL-1α and IL-1β differs in DSS-induced colitis in that IL-1α, mainly of colon epithelial cells is inflammatory, whereas IL-1β, mainly of myeloid cell origin, promotes healing and repair. Given the dissimilar functions of each IL-1 agonistic molecule, an IL-1 receptor blockade would not be as therapeutically effective as specific neutralising of IL-1α, which leaves IL-1β function intact. ER -