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Original article
Non-redundant properties of IL-1α and IL-1β during acute colon inflammation in mice
  1. Marina Bersudsky1,
  2. Lotem Luski1,
  3. Daniel Fishman2,
  4. Rosalyn M White1,
  5. Nadya Ziv-Sokolovskaya3,
  6. Shahar Dotan1,
  7. Peleg Rider1,
  8. Irena Kaplanov1,
  9. Tegest Aychek4,
  10. Charles A Dinarello5,
  11. Ron N Apte1,
  12. Elena Voronov1
  1. 1Faculty of Health Sciences, The Shraga Segal Department of Microbiology and Immunology and The Cancer Research Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel
  2. 2Department of Morphology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
  3. 3Pathology Department, Kaplan Medical Center, Rehovot, Israel
  4. 4Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel
  5. 5Department of Medicine, University of Colorado Denver, Aurora, Colorado, USA
  1. Correspondence to Dr Elena Voronov, Faculty of Health Sciences, The Shraga Segal Department of Microbiology and Immunology and The Cancer Research Center, Beer-Sheva 84105, Israel; elena{at}bgu.ac.il

Abstract

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.

  • INTESTINAL EPITHELIUM
  • EXPERIMENTAL COLITIS
  • GUT INFLAMMATION
  • INTERLEUKINS
  • MUCOSAL IMMUNITY

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