title: Non-redundant properties of IL-1α and IL-1β during acute colon inflammation in mice.
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.
  
  
  METHODS
  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.
authors.affiliation: Faculty 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.
authors.forename: Marina
authors.initials: M
authors.lastname: Bersudsky
authors.forename: Lotem
authors.initials: L
authors.lastname: Luski
authors.forename: Daniel
authors.initials: D
authors.lastname: Fishman
authors.forename: Rosalyn M
authors.initials: RM
authors.lastname: White
authors.forename: Nadya
authors.initials: N
authors.lastname: Ziv-Sokolovskaya
authors.forename: Shahar
authors.initials: S
authors.lastname: Dotan
authors.forename: Peleg
authors.initials: P
authors.lastname: Rider
authors.forename: Irena
authors.initials: I
authors.lastname: Kaplanov
authors.forename: Tegest
authors.initials: T
authors.lastname: Aychek
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.forename: Ron N
authors.initials: RN
authors.lastname: Apte
authors.forename: Elena
authors.initials: E
authors.lastname: Voronov
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D003106:Colon / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016264:Dextran Sulfate / Q000494:pharmacology; D004195:Disease Models, Animal; D007375:Interleukin-1 / Q000819:agonists; D053582:Interleukin-1alpha / Q000502:physiology*; D053583:Interleukin-1beta / Q000502:physiology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D017254:Leukemic Infiltration / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: D007375:Interleukin-1; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D016264:Dextran Sulfate
keywords: EXPERIMENTAL COLITIS; GUT INFLAMMATION; INTERLEUKINS; INTESTINAL EPITHELIUM; MUCOSAL IMMUNITY