Interleukin 1 is a key driver of inflammatory bowel disease-demonstration in a murine IL-1Ra knockout model.

ABSTRACT: Interleukin 1 (IL-1) is an important mediator of inflammation and tissue damage in inflammatory bowel disease (IBD). The balance between IL-1 and IL-1Ra as a natural inhibitor plays a vital role in a variety of diseases. Here, we investigated whether changes seen during IBD are induced spontaneously in mice lacking a functional IL-1rn gene. Histological staining was performed on the jejunum and ileum of BALB/c IL-1rn^+/+ and IL-1rn^-/- mice to characterize crypt-villus height, villus width, and number of goblet cells per villus. Pro-inflammatory cytokines, immune cell infiltration and matrix-degrading enzymes, together with the production of intestinal enzymes and the integrity of tight and adherent junction proteins were determined using immunohistochemistry. In the small intestine of BALB/c IL-1rn^-/- mice the villus heights were significantly reduced; and in the ileum this was accompanied by a decrease in villi width. There was also an increase in goblet cell number and mucin production compared to wild-type mice. IL-1? and IL-1? immunopositivity were increased, whilst IL-1R1 expression was decreased in IL-1rn^-/- mice. IL-15 and TNF? were also increased in older IL-1rn^-/- mice. Increased polymorphonuclear and macrophage infiltration were seen in IL-1rn^-/- mice, whilst expression of matrix-degrading enzymes and digestive enzymes were unchanged, except for dipeptidyl peptidase IV which was increased in younger IL-1rn^-/- mice compared to wild type mice. The expression of tight and adhesion junctions were also dramatically decreased in IL-1rn^-/- mice. In conclusion, IL-1rn^-/- mice developed spontaneous abnormalities which displayed features associated with IBD, demonstrating a clear role for IL-1 in IBD.

SUBMITTER: Dosh RH 

PROVIDER: S-EPMC6544399 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature