IL-13

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Ligands
IL-13 (Human)

GtoPdb Ligand ID: 4980

Synonyms: hematopoietic growth factor | interleukin-13 | mast cell growth factor | multipotential colony-stimulating factor | P-cell-stimulating factor

Compound class: Endogenous peptide in human, mouse or rat

Comment: IL-13 shares sequence and structural homology with IL-4.

Species: Human

Immunopharmacology Comments
IL-13 is a mediator of allergic inflammation primarily secreted by T helper type 2 (Th2) cells [7] and has been strongly associated with induction of airway disease. The IL-13 receptor is a complex containing an IL-4Rα subunit and one or more IL-13-specific binding proteins (IL13RA1, IL13RA2). Ligand engagement of the IL-13R induces activation of the signal transducer and activator of transcription 6 (STAT6) transcription factor. Single nucleotide polymorphism rs1295686 identified in the IL-13 gene is linked to total serum immunoglobulin E (IgE) levels in asthmatics [4], and may also be associated with susceptibility for developing atopic dermatitis [5]. Anti-IL-13 monoclonal antibodies have been developed and evaluated in inflammatory airway diseases. Unfortunately this approach has not proven to produce clinically meaningful benefit in asthma or idiopathic pulmonary fibrosis (IPF) trials, and subsequently development of the most advanced biologics tralokinumab and lebrikizumab has been terminated [1]. A bispecific monoclonal targeting IL-13 and IL-4 (SAR156597, romilkimab) was designed with the aim of exploiting the synergistic action of simultaneously modulating the shared pathogenic activities of these two cytokines in lung inflammation. Having reached Phase 2, SAR156597 has reportedly failed to meet the primary endpoint in IPF, so further development in this condition has been halted [1]. Development of SAR156597 in diffuse systemic sclerosis is to continue (see Phase 2 NCT02921971).

Immunopharmacology Comments

IL-13 is a mediator of allergic inflammation primarily secreted by T helper type 2 (Th2) cells [7] and has been strongly associated with induction of airway disease. The IL-13 receptor is a complex containing an IL-4Rα subunit and one or more IL-13-specific binding proteins (IL13RA1, IL13RA2). Ligand engagement of the IL-13R induces activation of the signal transducer and activator of transcription 6 (STAT6) transcription factor.

Single nucleotide polymorphism rs1295686 identified in the IL-13 gene is linked to total serum immunoglobulin E (IgE) levels in asthmatics [4], and may also be associated with susceptibility for developing atopic dermatitis [5].

Anti-IL-13 monoclonal antibodies have been developed and evaluated in inflammatory airway diseases. Unfortunately this approach has not proven to produce clinically meaningful benefit in asthma or idiopathic pulmonary fibrosis (IPF) trials, and subsequently development of the most advanced biologics tralokinumab and lebrikizumab has been terminated [1]. A bispecific monoclonal targeting IL-13 and IL-4 (SAR156597, romilkimab) was designed with the aim of exploiting the synergistic action of simultaneously modulating the shared pathogenic activities of these two cytokines in lung inflammation. Having reached Phase 2, SAR156597 has reportedly failed to meet the primary endpoint in IPF, so further development in this condition has been halted [1]. Development of SAR156597 in diffuse systemic sclerosis is to continue (see Phase 2 NCT02921971).

Immunopharmacology Disease
Disease	X-Refs	Comment	References
Idiopathic pulmonary fibrosis	Disease Ontology: DOID:0050156 Orphanet: ORPHA2032	Failed clinical target for IPF and asthma.	1
Diffuse cutaneous systemic sclerosis	Orphanet: ORPHA220393	Drug target for diffuse systemic sclerosis- see Phase 2 trial NCT02921971 which is evaluating the anti-IL-4/IL-13 bispecific monoclonal antibody SAR156597.

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