Increased mucosal IL-12 expression is associated with relapse of ulcerative colitis

• Published in: BMC gastroenterology 2021-03, Vol.21 (1), p.122-122, Article 122
• Main Authors: Uchiyama, Kazuhiko, Takagi, Tomohisa, Mizushima, Katsura, Kajiwara-Kubota, Mariko, Kashiwagi, Saori, Toyokawa, Yuki, Tanaka, Makoto, Hotta, Yuma, Kamada, Kazuhiro, Ishikawa, Takeshi, Konishi, Hideyuki, Kishimoto, Mitsuo, Naito, Yuji, Itoh, Yoshito
• Format: Article
• Language: English
• Subjects: Biopsy; Colitis, Ulcerative - genetics; Colonoscopy; Cytokines; Dendritic cells; Development and progression; Disease; Diseases; Endoscopy; Gastroenterology; Gene expression; Health aspects; Humans; IL-12; IL-23; Inflammation; Inflammatory bowel disease; Interleukin 12; Interleukin 23; Interleukin-12 - genetics; Intestinal Mucosa; Mucosa; Pathogenesis; Patients; Rectal mucosa; Rectum; Recurrence; Relapse; Remission; Risk factors; Severity of Illness Index; Ulcerative colitis; Variance analysis; γ-Interferon
• ISSN: 1471-230X; 1471-230X
• DOI: 10.1186/s12876-021-01709-5

The role of IL-12/23 in the pathogenesis of ulcerative colitis (UC) is unclear. We analyzed mucosal IL-12/23 expression and its relationship with endoscopic severity, histological activity, and UC relapse. Rectal biopsies were collected from 70 UC patients with clinical remission. IL-12, IL-23, IFN-γ, IL-17A, and IL-17F mRNA expression was measured by real-time PCR. Endoscopic severity and histological activity were evaluated using the Mayo endoscopic subscore (MES) and the Geboes score, respectively. The longest follow-up period was 51 months. Thirty-four patients relapsed during the study period. Samples from these subsequently relapsed patients formed the "relapse" group, while those from patients that did not relapse formed the "remission" group. IL-12 (P = 0.0003) and IL-23 (P = 0.014) mRNA expression was significantly higher in the relapse than the remission group. Expression of IL-23 (P = 0.015) but not IL-12 (P = 0.374) was correlated with MES. However, in patients with an MES of 0 and 1, IL-12 expression was statistically higher in the relapse than the remission group (P = 0.0015, P = 0.0342). IL-12 and IL-23 expression did not vary significantly between histologically active and inactive mucosa; both were higher in histologically inactive patients in the remission group (IL-12: P = 0.0002, IL-23: P = 0.046). Rectal IL-12 and IL-23 expression was elevated in the relapse group, but IL-12 was more strongly associated with UC relapse, irrespective of endoscopic severity and histological activity. Mucosal IL-12 was elevated in patients with deep mucosal healing. Our results suggest an important role of IL-12 in UC pathogenesis and the molecular mechanism of UC relapse.