Interleukin (IL)-33: New therapeutic target for atopic diseases

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 glucocorticoidresistant 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. © the japanese pharmacological society.