Expression of Interleukin-12-Related Cytokine Transcripts in Inflammatory Bowel Disease: Elevated Interleukin-23p19 and Interleukin-27p28 in Crohn's Disease But Not in Ulcerative Colitis

• Published in: Inflammatory bowel diseases Vol. 11; no. 1; pp. 16 - 23
• Main Authors: Schmidt, Carsten, Giese, Thomas, Ludwig, Bianca, Mueller-Molaian, Ina, Marth, Thomas, Zeuzem, Stefan, Meuer, Stefan C., Stallmach, Andreas
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford University Press 01.01.2005; Lippincott Williams & Wilkins, Inc
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Case-Control Studies; Colitis, Ulcerative - genetics; Colitis, Ulcerative - metabolism; Crohn Disease - genetics; Crohn Disease - metabolism; Crohn's disease; Cytokines; Female; Humans; Inflammatory bowel disease; Interleukin-23; Interleukin-23 Subunit p19; Interleukins - biosynthesis; Interleukins - genetics; interleukin‐27; Intestinal Mucosa; Male; Middle Aged; realtime polymerase chain reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; RNA, Messenger - biosynthesis; Transcription, Genetic; ulcerative colitis; Up-Regulation; Crohn's disease; ulcerative colitis; interleukin-27; realtime polymerase chain reaction; interleukin-23
• ISSN: 1078-0998; 1536-4844
• DOI: 10.1097/00054725-200501000-00003

BackgroundIt has been suggested that Crohn's disease (CD) is associated with an exaggerated T-helper 1 cytokine response manifested by increased production of interleukin (IL)-12. IL-12 is a heterodimeric protein comprising 2 disulfide-linked subunits designated p35 and p40. Recently, IL-12-related cytokines, IL-23 and IL-27, were described. Biologically active IL-23 is a heterodimer whose p40 subunit is identical to IL-12p40 whereas its p19 subunit is distantly related to IL-12p35. IL-27 consists of EBI3, an IL-12p40-related protein, and p28, a newly discovered IL-12p35-related polypeptide.AimWe sought to determine whether mucosal expression of IL-23p19 and IL-27p28 transcripts correlate with the inflammatory activity in inflammatory bowel disease (IBD).Patients/MethodsMessenger RNA expression in colonic mucosa from patients with Crohn's disease (CD; n = 37) and ulcerative colitis (UC; n = 19), and in non-IBD control subjects (specific colitis [SC]; n = 16) and normal, nondiseased control patients (n = 12) was measured by reverse-transcribed real-time polymerase chain reaction.ResultsIL-23p19 was significantly increased in inflamed mucosa in CD (P = 0.0377) and to a lesser extent also in UC patients but not in SC patients. Elevation of IL-23p19 transcript levels in CD correlated with the severity of endoscopic lesions. IL-27p28 transcripts and EBI3 transcripts were significantly elevated only in active CD.DiscussionIL-23p19, IL-27p28, and EBI3 transcripts are strongly up-regulated in CD. The stimulatory effects of these cytokines on naive T cells in addition to a strongly synergistic action with IL-12 to trigger interferon-γ production may contribute to the perpetuation of the inflammatory process in patients with CD. Notably, increased expression of IL-23 and IL-27 transcripts in CD suggests a T helper 1-dominated immunologic function in this disease.