IL-1β blockade prevents cell death and mucosal damage of the small intestine in a model of sterile inflammation

Abstract

The intestinal mucosa is covered by a layer of epithelial cells that is constantly challenged by commensal, opportunistic, and pathogenic microorganisms, their components, and harmful compounds. Any inflammatory response to these materials must be tightly controlled to limit tissue damage and restore the integrity of the mucosal barrier. We have shown previously that production of IL-1β via activation of the inflammasome can lead to mucosal damage in the small intestinal pathology that occurs after intragastric administration of a gluten derived peptide, p31-43. Here we show that specific inhibition of caspase-1 or NLRP3 abolishes the damage induced by p31-43, and that antibody-mediated blocking of IL-1β inhibits the both the histological changes and the induction of apoptosis and caspase-3 activation driven by p31-43. Understanding the role of IL-1β in sterile inflammation may help to understand chronic inflammatory pathological processes, and design new intervention strategies.

Keywords: Apoptosis; IL-1β; Inflammasome; Inflammation; Small intestine.