IL-33   Click here for help

GtoPdb Ligand ID: 5880

Synonyms: IL-1F11
Immunopharmacology Ligand
Compound class: Endogenous peptide in human, mouse or rat
Comment: IL-33 is a pleiotropic IL-1 family cytokine that can both promote type 2 inflammation and also drive immunoregulation through expansion of Foxp3+Treg cells. The outcomes of IL-33 activity appear to depend on the cells that produce it, either myeloid dendritic cells (DC) or epithelial cells [6]. DC-derived IL-33 supports Treg cells. The main cellular targets of IL-33 are innate lymphoid cells type 2 (ILC2), involved in the initiation of the type 2 immune response (secretion of IL-5 and IL-13) during parasitic infection and allergic diseases such as asthma. Full length IL-33 is cleaved by mast cell chymase (chymase 1; CMA1) to produce its significantly more active form [7].

The ST2/IL-33 axis is recognised as playing an important role in the development/exacerbation of IgE-dependent inflammations such as asthma and atopic dermatitis [1,5], and received much interest from the pharmaceutical industry. Blockade of IL-33 activity (and/or its receptor ST2) represent potential novel mechanisms for pharmaceutical intervention to suppress allergy and mast cell-eosinophil interplay. Indeed, astegolimab (RG6149/AMG 282) is an example of a fully human anti-IL-33 monoclonal antibody, that was developed as a potential therapy for mild atopic asthma and chronic rhinosinusitis. Unfortunalely, in common with other anti-IL-33 leads, RG6149 failed to deliver clinical efficacy in these indications.
Species: Human
Natural/Endogenous Targets
Target
Interleukin-33 receptor
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
Interleukin-33 receptor Ligand is endogenous in the given species Hs Agonist Agonist - - -
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Other ligands which bind to or alter the activity of this ligand
Key to terms and symbols Click column headers to sort
Ligand Sp. Type Action Value Parameter Concentration range (M) Reference
HpARI Peptide Mm Inhibitor Binding 9.3 pKd - 9
⤷ pKd 9.3 (Kd 5.6x10-10 M) [9]
Description: Evaluated by surface plasmon resonance (SPR).
HpARI Peptide Hs Inhibitor Binding 6.6 pKd - 9
⤷ pKd 6.6 (Kd 2.6x10-7 M) [9]
Description: Evaluated by surface plasmon resonance (SPR).
tozorakimab Peptide Hs Antibody Binding 10.1 pIC50 - 4
⤷ pIC50 10.1 (IC50 8.2x10-11 M) [4]
Description: Potency for binding between antibody and IL33red.