The Correlation between Interleukin-23 and Degree of Severity of Ulcerative Colitis

Abstract

Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis and colitis indeterminate. They cause intestinal swelling, inflammation and bleeding. Ulcerative colitis is a form of colitis that includes characteristic ulcers. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset, abdominal pain, and a variable group of "extra-intestinal" manifestations (such as arthritis, uveitis, skin changes), and the accumulation of inflammatory cells within the small intestine and colon. Symptoms can recur or be minimal for months and years. IBD results from the interaction between environmental, genetic and immune factors. Although environmental factors might be the triggers for the disorder, the predisposition to the disease is denoted by genetic and/or immune factors The incidence of ulcerative colitis is 1.2 to 20.3 cases per 100,000 persons per year, and its prevalence is 7.6 to 246.0 cases per 100,000 per year.The peak age of onset for UC is 15 to 30 years old, although it may occur at any age. About 10% of cases occur in individuals <18 years old. Interleukin 23 (IL-23) is a newly identified cytokine with increased expression in inflamed biopsies of colon mucosa in patients with ulcerative colitis. It is a heterodimeric cytokine comprised of two subunits, p19 which is unique to IL-23, and p40, which is shared with IL-12. IL-23 is produced by activated myeloid cells including macrophages and dendritic cells (DCs) following bacterial stimulation, or via CD40 signaling, and drives increases in a number of inflammatory cytokines in the intestine in the absence of T cells, including TNFα, IFNγ, IL6 and IL-17. IL-23-driven inflammation has primarily been linked to the actions of a new subset of T-helper cells namely T helper type 17. They not only play an important role in host defense against extracellular pathogens, but are also associated with the development of autoimmunity and inflammatory response such as inflammatory bowel disease (IBD). It is suggested that UC is mainly mediated through T helper 2 and natural killer cells. IL-23 promotes the development T helper 17 cells from mechanisms that are distinct from those of T helper 1. Recent studies have found increased expression of IL-23 in inflamed and noninflamed mucosa of patients with UC. The strong link between IL-23 and the Th17 response in vivo suggested that IL-23 was involved in the differentiation of Th17 cells. However, TGF-b and IL-6, rather than IL-23, were initially shown to be the key cytokines directing Th17 cell development. Subsequently, it was shown that other pro-inflammatory mediators such as IL-1 and IL-21 could substitute for IL-6 during Th17 differentiation.