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Description

IL-11 Antibodies: Mechanism and Development

IL-11 antibodies neutralize the cytokine IL-11, which is implicated in fibrotic diseases (e.g., idiopathic pulmonary fibrosis, liver cirrhosis) and aging .

Mechanism of Action

IL-11 signals through the IL-11 receptor (IL-11Rα), activating pathways like ERK-mTORC1 and JAK-STAT3, promoting fibrosis and senescence . Antibodies block these pathways, mitigating tissue damage .

Development and Specificity

Antibody Type	Target	Cross-Reactivity	Application
Anti-IL-11 (e.g., X203)	IL-11 protein	<2.8% (CLIN/PIR)	Fibrosis, aging models
Anti-IL-11Rα (e.g., X209)	IL-11Rα receptor	N/A	Fibrosis, liver injury
1B11 (lincomycin)	Lincomycin	2.8% (CLIN)	Drug residue detection

Fibrosis Treatment

IL-11 antibodies (e.g., X203) reduce collagen deposition and epithelial-to-mesenchymal transition (EMT) in lung, liver, and kidney fibrosis models . For example:

Lung Fibrosis: X203 inhibits ERK/SMAD signaling, reducing myofibroblast activation .
Liver Fibrosis: Combined with dietary interventions, X203 reverses fibrosis in NASH models .

Aging and Lifespan Extension

In mice, anti-IL-11 therapy (X203) extends median lifespan by 22–25% (120 → 155 weeks), reducing frailty, metabolic decline, and cancer incidence . Key effects include:

Parameter	Wild-Type Mice	IL-11 Antibody-Treated Mice
Median Lifespan	120 weeks	155 weeks
Fat Mass (Old Age)	↑	↓
Lean Mass (Old Age)	↓	↑
Muscle Strength	↓	↑
Data from

Bioanalytical Assays for IL-11 Detection

Ultra-sensitive assays (e.g., Simoa Planar Array) enable precise quantification of free IL-11 in plasma, critical for tracking therapeutic efficacy .

Assay Platform	Lower Limit of Quantitation (LLOQ)	Application
Simoa Planar Array (SP-X)	0.006 pg/mL	PK/PD modeling in mice/humans
Meso Scale Discovery	N/A	Epitope mapping

Challenges and Future Directions

Cross-Species Specificity: IL-11 antibodies (e.g., X203) must be engineered for human IL-11Rα binding .
Clinical Trials: Phase 1 trials are ongoing for anti-IL-11 (9MW3811, BI 765423) and anti-IL-11Rα (LASN01) antibodies in fibrotic diseases .

Product Specs

Buffer

Preservative: 0.03% Proclin 300
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4

Form

Liquid

Lead Time

Made-to-order (14-16 weeks)

Synonyms

lin-11 antibody; ZC247.3 antibody; Protein lin-11 antibody; Abnormal cell lineage protein 11 antibody

Target Names

lin-11

Uniprot No.

P20154

Target Background

Function

LIN-11 is a probable transcription factor essential for the asymmetric division of vulval blast cells. It plays a role in olfactory plasticity, likely by regulating the expression of the transcription factor mbr-1 in RIF neurons. Additionally, LIN-11 contributes to the chemorepulsive response towards ascaroside pheromones mediated by the ADL sensory neurons, potentially by regulating E-box motif 5'-CANNTG-3' containing target genes in these neurons. Furthermore, LIN-11 is involved in the differentiation of ADL sensory neurons.

Gene References Into Functions

Multiple factors cooperate to regulate the pi-specific expression of lin-11, and together with other findings, suggest that the mechanism of lin-11 regulation by LIN-12/Notch signaling is evolutionarily conserved in Caenorhabditis species. PMID: 18950616

Database Links

KEGG: cel:CELE_ZC247.3

STRING: 6239.ZC247.3

UniGene: Cel.18452

Subcellular Location

Nucleus.

Tissue Specificity

Expressed in ADL, AVJL, AIZL, RICL, RIF and AVG neurons.

Q&A

FAQs for Researchers on IL-11 Antibody (X203 Clone) in Academic Research
Compiled from peer-reviewed studies, patents, and preprint data (2018–2025)

Advanced Research Questions

How to resolve contradictions in IL-11’s role in VSMC proliferation?

Early studies suggested IL-11 inhibits VSMC growth, but recent data show pro-proliferative effects in injury models .

Key factor: Recombinant human IL-11 (rhIL-11) acts as a competitive inhibitor of mouse IL-11, confounding earlier results .
Methodological fix: Use species-matched antibodies (e.g., X203 targets mouse IL-11) and validate via:
- RNAscope® to localize IL-11RA expression in VSMCs.
- Co-culture assays with TGFβ1/ANGII stimulation .

How to optimize IL-11 antibodies for dual targeting of fibrosis and hyperplasia?

Epitope engineering: Target IL-11 residues 22–199 (X203’s binding site) to block receptor docking .
Mutagenesis strategies:
- Use structure-guided libraries (e.g., Trastuzumab CDR3 mutagenesis) with ≤4 mutations from wild type .
- Apply multi-objective linear programming to balance affinity (ΔΔG ≤ −1.5 kcal/mol) and humanness (≥85% human germline similarity) .

What in silico methods improve antibody library design for IL-11 targeting?

Method	Advantages	Limitations
Deep mutational scanning	Predicts ΔΔG for 10⁴ variants in 48 hrs	Requires antibody-antigen co-crystal structure
Diversity-constrained ILP	Ensures batch diversity (≥0.8 Shannon index)	Computationally intensive for >1,000 variants

Data Contradiction Analysis

Conflicting finding: IL-11 inhibition reduces collagen in uninjured arteries (−32% vs. IgG) but has no effect on macrophage infiltration .

Resolution:
- Perform single-cell RNA sequencing to identify IL-11-responsive fibroblast subsets.
- Use MMP2⁻/⁻ mice to isolate collagen regulation pathways .

Methodological Best Practices

In vivo validation: Pair ultrasound (↓0.12 mm vessel wall thickness) with multiplex IHC (α-SMA⁺/SM22α⁺ ratios) .
Library design: For every 10 variants, enforce ≤2 mutations at any single position and ≥3 Hamming distance between sequences .

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lin-11 Antibody