Document Detail


Suppression of inflammation in ulcerative colitis by interferon-β-1a is accompanied by inhibition of IL-13 production.
MedLine Citation:
PMID:  20971977     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Peter J Mannon; Ronald L Hornung; Zhiqiong Yang; Chuli Yi; Catherine Groden; Julia Friend; Michael Yao; Warren Strober; Ivan J Fuss
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural     Date:  2010-10-22
Journal Detail:
Title:  Gut     Volume:  60     ISSN:  1468-3288     ISO Abbreviation:  Gut     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-07     Completed Date:  2011-04-25     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  2985108R     Medline TA:  Gut     Country:  England    
Other Details:
Languages:  eng     Pagination:  449-55     Citation Subset:  AIM; IM    
Affiliation:
Mucosal Immunity Section, Laboratory of Host Defense, NIAID, NIH, Bethesda, Maryland, USA. pmannon@uab.edu
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
CD4-Positive T-Lymphocytes / immunology
Cells, Cultured
Colitis, Ulcerative / drug therapy*,  immunology
Cytokines / biosynthesis
Female
Follow-Up Studies
Gastrointestinal Agents / adverse effects,  therapeutic use*
Humans
Interferon-beta / adverse effects,  therapeutic use*
Interleukin-13 / biosynthesis*
Male
Middle Aged
Treatment Outcome
Young Adult
Grant Support
ID/Acronym/Agency:
N01-CO-12400/CO/NCI NIH HHS; Z01 AI000903-07/AI/NIAID NIH HHS; ZIA AI000903-09/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Cytokines; 0/Gastrointestinal Agents; 0/Interleukin-13; 145258-61-3/interferon beta 1a; 77238-31-4/Interferon-beta
Comments/Corrections
Comment In:
Gut. 2011 Apr;60(4):430-1   [PMID:  21266724 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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