OBJECTIVE: Ulcerative colitis is associated with increased interleukin 13 (IL-13) production by natural killer T cells. Taking advantage of the inhibitory actions of interferon β on IL-13 expression, this proof-of-concept study aimed to show that decreasing IL-13 production is associated with clinical improvement of ulcerative colitis symptoms. DESIGN: Open-label interventional drug trial. SETTING: Outpatient clinical research hospital. Patients Adult patients with active ulcerative colitis (Short Clinical Colitis Activity Index (SCCAI)≥ 5). Interventions Treatment with 30 μg IM interferon-β-1a (Avonex) weekly for 12 weeks with 6 month follow-up. MAIN OUTCOME MEASURES: Clinical response was defined as ≥ 3 point drop in the SCCAI for at least two consecutive monitoring visits, and cytokine production was measured in cultured peripheral blood and lamina propria mononuclear cells (LPMC) before and after treatment. RESULTS: 11 of 16 patients were clinical responders, and 4 were in remission (SCCAI ≤ 2) at the end of treatment. Rectal bleeding subscores improved dramatically by week 4 (38% with frank bleeding vs 87% pretreatment). Increased IL-13 production by LPMC T cells fell significantly in clinical responders (690 ± 99 vs 297 ± 58 pg/ml p = 0.015) but was unchanged in non-responders (542 ± 83 vs 510 ± 39 pg/ml). In addition, non-responders had significantly higher production of IL-17 and IL-6 pre-treatment compared to responders. CONCLUSIONS: Interferon-β-1a induces clinical response and remission in a large subset of patients with ulcerative colitis that is associated with significant inhibition of IL-13 production. In addition, increased IL-17 and IL-6 production is associated with no response to interferon-β. These data provide a proof-of-concept that IL-13 is an effector cytokine in ulcerative colitis and should be a target for novel therapies.
OBJECTIVE:Ulcerative colitis is associated with increased interleukin 13 (IL-13) production by natural killer T cells. Taking advantage of the inhibitory actions of interferon β on IL-13 expression, this proof-of-concept study aimed to show that decreasing IL-13 production is associated with clinical improvement of ulcerative colitis symptoms. DESIGN: Open-label interventional drug trial. SETTING:Outpatient clinical research hospital. Patients Adult patients with active ulcerative colitis (Short Clinical Colitis Activity Index (SCCAI)≥ 5). Interventions Treatment with 30 μg IM interferon-β-1a (Avonex) weekly for 12 weeks with 6 month follow-up. MAIN OUTCOME MEASURES: Clinical response was defined as ≥ 3 point drop in the SCCAI for at least two consecutive monitoring visits, and cytokine production was measured in cultured peripheral blood and lamina propria mononuclear cells (LPMC) before and after treatment. RESULTS: 11 of 16 patients were clinical responders, and 4 were in remission (SCCAI ≤ 2) at the end of treatment. Rectal bleeding subscores improved dramatically by week 4 (38% with frank bleeding vs 87% pretreatment). Increased IL-13 production by LPMC T cells fell significantly in clinical responders (690 ± 99 vs 297 ± 58 pg/ml p = 0.015) but was unchanged in non-responders (542 ± 83 vs 510 ± 39 pg/ml). In addition, non-responders had significantly higher production of IL-17 and IL-6 pre-treatment compared to responders. CONCLUSIONS: Interferon-β-1a induces clinical response and remission in a large subset of patients with ulcerative colitis that is associated with significant inhibition of IL-13 production. In addition, increased IL-17 and IL-6 production is associated with no response to interferon-β. These data provide a proof-of-concept that IL-13 is an effector cytokine in ulcerative colitis and should be a target for novel therapies.
Authors: Ivan J Fuss; Frank Heller; Monica Boirivant; Francisco Leon; Masaru Yoshida; Stefan Fichtner-Feigl; Zhiqiong Yang; Mark Exley; Atsushi Kitani; Richard S Blumberg; Peter Mannon; Warren Strober Journal: J Clin Invest Date: 2004-05 Impact factor: 14.808
Authors: H Tilg; H Vogelsang; O Ludwiczek; H Lochs; A Kaser; J-F Colombel; H Ulmer; P Rutgeerts; S Krüger; A Cortot; G D'Haens; M Harrer; C Gasche; F Wrba; I Kuhn; W Reinisch Journal: Gut Date: 2003-12 Impact factor: 23.059
Authors: M J Aman; T Tretter; I Eisenbeis; G Bug; T Decker; W E Aulitzky; H Tilg; C Huber; C Peschel Journal: Blood Date: 1996-06-01 Impact factor: 22.113
Authors: M K Levings; R Sangregorio; F Galbiati; S Squadrone; R de Waal Malefyt; M G Roncarolo Journal: J Immunol Date: 2001-05-01 Impact factor: 5.422
Authors: Michael J Rosen; Rebekah Karns; Jefferson E Vallance; Ramona Bezold; Amanda Waddell; Margaret H Collins; Yael Haberman; Phillip Minar; Robert N Baldassano; Jeffrey S Hyams; Susan S Baker; Richard Kellermayer; Joshua D Noe; Anne M Griffiths; Joel R Rosh; Wallace V Crandall; Melvin B Heyman; David R Mack; Michael D Kappelman; James Markowitz; Dedrick E Moulton; Neal S Leleiko; Thomas D Walters; Subra Kugathasan; Keith T Wilson; Simon P Hogan; Lee A Denson Journal: Gastroenterology Date: 2017-01-26 Impact factor: 22.682