Fig. 7.

Graphical summary of anti–IL-1α effects in chronic intestinal inflammation. During spontaneous ileitis (Left) and experimental DSS-induced colitis (Right), damaged intestinal epithelial cells (IECs) release large amounts of IL-1α. In turn, IL-1α stimulates the production of IL-1β and other mediators of inflammation (e.g., Cox2, MPO), leading to increased disease, dysbiosis, and epithelial barrier disruption. Following IL-1α blockade with an anti–IL-1α murine-specific monoclonal antibody (FLO1 mAb), the severity of ileitis and colitis is dramatically reduced, along with diminished titer of inflammatory markers (IL-1α, IL-1β, MPO, COX2) and increased levels of IL-18, which is an inducer of intestinal barrier integrity. More importantly, IL-1α blockade is associated with changes in microbiota community structures, including higher abundance of probiotic strains, which may be of translational interest for patients that can potentially benefit from IL-1α therapy.