IL-33 and IL-18 in Inflammatory Bowel Disease Etiology and Microbial Interactions

The IL-1 cytokines are a newly expanded family, with each of its 11 members playing an important role in health and disease. Typically acting as pro- or anti-inflammatory mediators of first-line innate immunity, their production is particularly important in the context of mucosal defenses, through handling breach of the delicate epithelial barrier and mediating a local immune response to invading pathogens. Mucosal immunity is often aberrantly orchestrated in intestinal diseases, such as Inflammatory Bowel Disease (IBD). Various studies have pointed to IL-1 cytokines as being important players in IBD with context-dependent roles, either through promoting auto-inflammatory mechanisms, or alleviating disease through protection against breach of pathogens across the epithelial barrier. This mini-review will succinctly examine the role of IL-1 family members in IBD, with a special focus on the recently described IL-33 as well as IL-18, and will explore the disease models within which these cytokines have been studied. Furthermore, we will examine the evidence of interplay of these cytokines with the gut microbiota, with hopes of summarizing our current knowledge of these family members and their potential for unraveling novel molecular mechanisms of IBD pathology.