IL-11 in fibrostenotic Crohn’s disease: historical agonism, the selective-inhibition hypothesis, and evidence thresholds for translation
- 1The Fourth People’s Hospital of Shenyang
Abstract
Effective medical treatment for fibrostenotic Crohn’s disease remains a major unmet clinical need. This narrative review examines whether high stromal interleukin-11 (IL-11) identifies a pharmacologically reversible dependency in established fibrostenotic disease or mainly marks advanced remodeling. Historical trials found schedule-dependent activity of recombinant human IL-11, but an active-comparator trial showed inferior remission induction compared with prednisolone. In mice, Il11 or Il11ra1 deficiency worsened epithelial apoptosis and acute dextran sulfate sodium (DSS) colitis. By contrast, inducible Il11 deletion during repeated DSS injury reduced collagen deposition and hydroxyproline with broadly similar inflammatory trajectories. These contrasting findings support context-dependent effects across acute injury and chronic remodeling. Human tissue, serum and treatment-response studies associate IL-11 with fibrostenosis and stromal activation, but do not establish that an IL-11-high lesion responds to selective inhibition. Differences in fibroblast state, tissue compartment and treatment timing could therefore influence both efficacy and harm. Early LASN01 studies outside inflammatory bowel disease support systemic target engagement and preliminary tolerability; intestinal efficacy remains untested. The decisive next test is selective inhibition after a structural lesion is documented, with verified intestinal exposure and separate structural, inflammatory and repair outcomes. This would distinguish reduced collagen accumulation during disease development from reversal of an established Crohn’s stricture.
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BibTeX
@article{chen2026il11,
title = {{IL-11 in fibrostenotic Crohn’s disease: historical agonism, the selective-inhibition hypothesis, and evidence thresholds for translation}},
author = {He Chen and Shuang Liang},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1951110},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1951110/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - IL-11 in fibrostenotic Crohn’s disease: historical agonism, the selective-inhibition hypothesis, and evidence thresholds for translation
AU - He Chen
AU - Shuang Liang
PY - 2026
DA - 2026/10/16
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1951110
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1951110/full
AB - Effective medical treatment for fibrostenotic Crohn’s disease remains a major unmet clinical need. This narrative review examines whether high stromal interleukin-11 (IL-11) identifies a pharmacologically reversible dependency in established fibrostenotic disease or mainly marks advanced remodeling. Historical trials found schedule-dependent activity of recombinant human IL-11, but an active-comparator trial showed inferior remission induction compared with prednisolone. In mice, Il11 or Il11ra1 deficiency worsened epithelial apoptosis and acute dextran sulfate sodium (DSS) colitis. By contrast, inducible Il11 deletion during repeated DSS injury reduced collagen deposition and hydroxyproline with broadly similar inflammatory trajectories. These contrasting findings support context-dependent effects across acute injury and chronic remodeling. Human tissue, serum and treatment-response studies associate IL-11 with fibrostenosis and stromal activation, but do not establish that an IL-11-high lesion responds to selective inhibition. Differences in fibroblast state, tissue compartment and treatment timing could therefore influence both efficacy and harm. Early LASN01 studies outside inflammatory bowel disease support systemic target engagement and preliminary tolerability; intestinal efficacy remains untested. The decisive next test is selective inhibition after a structural lesion is documented, with verified intestinal exposure and separate structural, inflammatory and repair outcomes. This would distinguish reduced collagen accumulation during disease development from reversal of an established Crohn’s stricture.
SN - 1663-9812
ER -