Inflammatory Bowel Disease Mucosal Biopsies Have Specialized Lymphokine mRNA Profiles

Abstract

: Crohn's disease (CD) and ulcerative colitis (UC) are idiopathic inflammatory bowel diseases (IBD) that are characterized by chronic intestinal inflammation and are associated with abnormalities of peripheral and mucosal immune function. The aim of our study was to determine whether CD or UC is characterized by discrete profiles of intestinal lymphokine production. Total cellular RNA was isolated from biopsies of healthy controls and from patients with IBD. Messenger RNA transcript levels in biopsies were determined for interleukin-2 (IL-2), IL-4, IL-5, and interferon-γ (IFN-γ), using a quantitative reverse transcriptase polymerase chain reaction method. Compared with inflamed UC mucosa and controls, CD mucosal lesions contained higher IL-2 and IFN-γ mRNA (p < 0.05), which is consistent with a T-helper cell 1 (Th1)-like pattern. In UC, IL-5 mRNA content was higher in involved areas compared with controls (p < 0.05) and inflamed CD lesions (p < 0.05), suggestive of a Th2 pattern. We conclude that the intestinal mucosa of CD and UC have inflammatory responses characterized by discrete T-helper profiles of lymphokines. This strongly suggests that the immunopathogenesis of these two forms of IBD are different.

Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines

“…Some IBD patients have a decreased mucosal IL-4 production [26] and in some experimental colitis models, such as in IL-2 knockout mice [27], IL-4 production is down-regulated. In contrast to CD, UC has no such typical Th1 cytokine pattern [23,28]. In DSS-induced colitis, a UC-like model, IL-4 secretion is up-regulated during its chronic phase.…”

Peripheral Blood Intracellular Cytokine Analysis in Children Newly Diagnosed with Inflammatory Bowel Disease

“…These results represent measurement of cytokine from more than lymphocytes (total mRNA of lymphocytes and macrophages). Patient details in the study by Mullin et al (4) are not given, but in the study of Camoglio et al (5), the mean duration of disease was greater than 6 y and the mean age of the patient was older than 32 y. In a study of surgical resection specimens obtained from adult patients, which evaluated enriched CD4 ϩ T cells, IFN-␥ secretion by both freshly isolated lamina propria and peripheral blood CD4 ϩ T cells was found to be increased compared with CD4 ϩ T cells from UC patients and control subjects (6).…”

“…In UC, total mRNA analysis from biopsy specimens have revealed higher IL-4 expression levels in actively inflamed mucosa compared with noninflamed UC mucosa and that from non-UC inflamed mucosa (8) or showed a trend but no statistical difference (4). In other studies of older patients with previously established CD or UC and taking various medications, decreased production of IL-4 from isolated lamina propria CD4 ϩ T cells or mononuclear cells compared with control subjects was determined (6,7).…”

Lamina Propria Mononuclear Cells Express and Respond to Interleukin-2 Differently in Crohn's Disease and Ulcerative Colitis.

“…The involvement of T helper subsets was also suggested by Yamamuraet al in the study of humanleprosy lesions in which the selected expression ofThl or Th2 cytokines is critical to the formation of the characteristic disease, tuberculoid or lepromatous lesions, respectively (26). Since the proportion of cells positive for the conventional cell surface marker for helper T cells (CD4+, 2H4" cells) was similar between CD and UC LPMC (8,27), the future development of cell surface markers which distinguish Thl and Th2-like cells will clarify whether abnormalities of mucosal helper T cell subsets are associated with the pathogenesis of IBD (20). Increasing evidence suggests the involvement of T cells in the pathogenesis of CD.…”