Suppression of inflammation in ulcerative colitis by interferon-β-1a is accompanied by inhibition of IL-13 production.
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.


METHODS
Open-label interventional drug trial.


METHODS
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.


METHODS
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.
Mannon
Peter J
PJ
Mucosal Immunity Section, Laboratory of Host Defense, NIAID, NIH, Bethesda, Maryland, USA. pmannon@uab.edu
Hornung
Ronald L
RL
Yang
Zhiqiong
Z
Yi
Chuli
C
Groden
Catherine
C
Friend
Julia
J
Yao
Michael
M
Strober
Warren
W
Fuss
Ivan J
IJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005500:Follow-Up Studies; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000009:adverse effects / Q000627:therapeutic use*; D018793:Interleukin-13 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
D016207:Cytokines; D005765:Gastrointestinal Agents; D018793:Interleukin-13; D016899:Interferon-beta; D000068556:Interferon beta-1a