Anti-IL-33 Neutralizing Antibody

IL-33 is a cytokine of the IL-1 family that is released in response to external triggers, such as trauma, allergen exposure and infections. IL-33 can be either in a reduced or oxidized state, which use different signaling pathways. When in its reduced state (IL-33red) it binds to IL-1RL1 ((interleukin 1 receptor like 1), also named IL-33R or ST2 (receptor serum-stimulated 2) . IL-1RL1 exists as both a membrane bound protein or a truncated soluble form. Binding of IL-33 to IL-1RL1 initiates a signaling pathway that involves NF-κF (nuclear factor kappa-light-chain-enhancer of activated B cells) and MAPK (mitogen-activated protein kinase), and results in release of pro-inflammatory cytokine and chemokines. The soluble form of IL-1RL1 can act as a decoy receptor for IL-33. Dysregulation in the levels of IL-33 is implicated in the pathology of inflammatory and infectious diseases, including COVID-19, COPD (chronic obstructive pulmonary disease) and asthma. The involvement of IL-33 in these diseases has made it a high value therapeutic target, with strategies such as antibodies being developed to inhibit the binding of IL-33 to its receptor. One example is Tozorakimab (MEDI3506), from AstraZeneca, currently being evaluated as treatment for COPD. Further studies on IL-33 and its receptor will likely result in new therapies for IL-33 related disorders.