Interleukin-4, Interleukin-13, Interleukin-33 (IL-4, IL-13, IL-33)

Interleukin-4, interleukin-13, and interleukin-33 are pivotal cytokines that regulate immune and inflammatory responses. IL-4 and IL-13 are structurally and functionally related; they induce B-cell class switching to IgE, promote Th2 differentiation, regulate airway and tissue remodeling, and drive allergic inflammation. IL-4 and IL-13 signal primarily via the type I and type II cytokine receptor complexes (involving IL-4Rα and IL-13Rα1), activating JAK/STAT and IRS pathways. IL-33 belongs to the IL-1 family of cytokines; it acts as an alarmin released from damaged epithelial or endothelial cells, signals through the ST2 (IL-1RL1) receptor, and modulates both pro- and anti-inflammatory responses in various tissues. Therapeutic targeting of these cytokines/receptors, especially with biologics like dupilumab, tralokinumab, and lebrikizumab, is established in allergic and fibrotic disease management, although overlapping functions and compensatory mechanisms remain a challenge for efficacy and safety[1][2][3][4][6][7][8].

Other names

IL4IL13IL33Th2 cytokinesAlarmin

Antibody antagonism of receptor (e.g., blocking IL-4Rα to inhibit IL-4/IL-13 signaling); Direct cytokine neutralization (anti-IL-13 antibodies); Inhibition of receptor-ligand binding prevents JAK/STAT pathway activation; Blockade of IL-33-ST2 (IL-1RL1) signaling.