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Additional IL-1 family signaling axes including IL1RL1, IL1RL2, IL23R , and IL18R1 are associated with neutrophilic and severe airway inflammation, helping to define disease endotypes (106109) RORA is necessary for development of the Th2-mediated allergic response (110), IL-6R signaling correlates with disease severity and exacerbation frequency (111), the TNFSF15 axis links inflammation to airway remodeling and tissue damage (112), and ORMDL3 influences cytokine responses, cellular stress, and epithelial metabolic processes, contributing to a persistent inflammatory asthma phenotype (113)

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Different analogues have been obtained, depending on the degree of alkylation

& Drevet, J