Tozorakimab

IL33 is a cytokine of the IL1 family, that is released in response to external triggers, such as trauma, allergen exposure and infections. IL33 can be either on its reduced or oxidized state, which use different signaling pathways. When in its reduced state (IL33red) it binds to IL1RL1 ((interleukin 1 receptor like 1), also named IL33R or ST2 (receptor serum-stimulated 2) . IL1RL1 exists as both a membrane bound protein or a truncated soluble form. Binding of IL33 to IL1RL1 initiated 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 IL1RL1 can act as a decoy receptor for IL33. Dysregulation in the levels of IL33 is implicated in the pathology of inflammatory and infectious diseases, including COVID-19, COPD (chronic obstructive pulmonary disease) and asthma. The involvement of IL33 in these diseases has made it a high value therapeutic target, with strategies such as antibodies being developed to inhibit the binding of IL33 to its receptor. One example is tozorakimab (MEDI3506), from AstraZeneca, currently being evaluated as treatment for COPD. Further studies on IL33 and its receptor will likely result in new therapies for IL33 related disorders.