title: Interleukin (IL)-33: new therapeutic target for atopic diseases.
abstract: Interleukin (IL)-33, a member of the IL-1 family of cytokines, is produced when epithelial and endothelial cells are exposed to stimuli. Hematopoietic cells such as macrophages also produce IL-33. IL-33 is considered to function as an 'alarmin', activating various immune cells through its receptor ST2, which leads to the production of various molecules. The IL-33-induced production of pro-inflammatory cytokines is a critical event that aggravates atopic diseases such as asthma, atopic dermatitis, and pollenosis and suggests that IL-33-blocking agents could represent new therapeutic drugs. The anti-IL-33 antibody was effective in allergic models, whereas the anti-ST2 antibody has yielded controversial results because soluble ST2 functions as a decoy receptor for IL-33. IL-33-mediated pulmonary inflammation may be glucocorticoid-resistant especially when other cytokines act synergistically. Anti-tumor necrosis factor (TNF)-α therapy may also be effective against IL-33-mediated diseases. ERK1/2 inhibitors have also been shown to suppress the production of IL-33. On the other hand, activation of β2-receptors enhanced the expression of IL-33 mRNA in dendritic cells by activating protein kinase A (PKA), suggesting that PKA inhibitors may be candidates for IL-33-blocking agents. The effects of IL-33-blocking agents on atopic diseases need to be pharmacologically assessed in experimental and clinical studies.
authors.affiliation: Laboratory of Toxicology, Faculty of Pharmaceutical Sciences, Setsunan University, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nabe
mesh_terms: D018926:Anti-Allergic Agents / Q000627:therapeutic use*; D000906:Antibodies / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics*; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000627:therapeutic use; D008264:Macrophages / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D058990:Molecular Targeted Therapy; D011956:Receptors, Cell Surface / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D018926:Anti-Allergic Agents; D000906:Antibodies; D016207:Cytokines; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D018836:Inflammation Mediators; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D047908:Intracellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; C015482:protein kinase modulator; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1