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

Abstract

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.

Multi-method genome- and epigenome-wide studies of inflammatory protein levels in healthy older adults

“…Lastly, IL18R1 levels may also be causally associated with IBD. A number of studies have demonstrated that increased IL18 signalling confers detrimental effects in the context of gastrointestinal inflammatory processes [99].…”

Transcriptome Based Profiling of the Immune Cell Gene Signature in Rat Experimental Colitis and Human IBD Tissue Samples

“…Members of the IL-1 family, such as IL-1α, IL-1β and IL-18 have an important role in the regulation of tissue homeostasis, inflammatory response and immune cell activation [43,44]. Although IL-1α and IL-1β use the same IL-1R1 for binding, their expression pattern and function differ [43].…”

“…Bersudsky et al examined the effect of neutralizing antibodies against IL-1α, IL-1β and IL-1 receptor in DSS-induced colitis model and observed mitigation of inflammation after inhibition of IL-1α, whereas IL-1β blocking exacerbated the symptoms [46]. Similarly to IL-1β, IL-18 maturation is related to inflammasomes; moreover, NLRP6 inflammasome deficiency causes inadequate IL-18 production [44]. IL-18 plays a role in the activation of NK and Th1 cells, thereby, it is involved in tumor control; however, the overproduction of IL-18 enhances intestinal permeability [43].…”

Integrative omics approach to identify the molecular architecture of inflammatory protein levels in healthy older adults

“…Lastly, IL18R1 levels may also be causally associated with IBD. A number of studies have demonstrated that increased IL18 signalling confers detrimental effects in the context of gastrointestinal inflammatory processes (45).…”