Commentary: the role of the IL-18 system and other members of the IL-1R/TLR superfamily in innate mucosal immunity and the pathogenesis of inflammatory bowel disease: friend or foe?
Crohn's disease and ulcerative colitis are examples of inflammatory bowel disease (IBD), and are multifaceted chronic autoimmune disorders with unknown etiology; to date, there is no known cure. IBD is thought to occur as a result of an inappropriate immune response to environmental factors in a genetically predisposed host, and it has become increasingly clear that cytokines play an important role in this process. In recent years, several groups have provided evidence that IL-18 is significantly up-regulated during the course of chronic intestinal inflammation and appears to play a pivotal role in the pathogenesis of human IBD, particularly in Crohn's disease. IL-18 is a pleiotropic cytokine with several biological functions, but is most commonly associated with its ability to synergistically induce the expression of IFN-gamma. However, although IL-18 has been extensively studied in both human IBD as well as in murine models of colitis, no definitive function of IL-18 during the initiation and perpetuation of chronic gut inflammation has been firmly established, and its precise role in the pathogenesis of IBD has yet to be determined. In light of the recent observation that the transcription factor interferon regulatory factor-1 has the ability to regulate the functional activity of IL-18, and concomitantly disease severity, in a murine model of colitis through altered expression of its endogenous inhibitor, IL-18-binding protein, this commentary will review what is currently known regarding the role of IL-18 in normal mucosal immunity and during the pathogenesis of IBD.
Division of Gastroenterology and Hepatology, the Digestive Health Center of Excellence, University of Virginia Health System, Charlottesville 22908, USA.
Brian K
BK
Reuter
Theresa T
TT
Pizarro
D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D015212:Inflammatory Bowel Diseases / Q000209:etiology*; D050856:Interferon Regulatory Factor-1; D020382:Interleukin-18 / Q000502:physiology*; D007422:Intestines / Q000276:immunology; D008562:Membrane Glycoproteins / Q000502:physiology*; D010750:Phosphoproteins / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D017472:Receptors, Interleukin-1 / Q000502:physiology*; D051193:Toll-Like Receptors
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D020382:Interleukin-18; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D011956:Receptors, Cell Surface; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors